NM_001144950.2:c.3931C>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001144950.2(SSC5D):c.3931C>G(p.Pro1311Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00040 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SSC5D
NM_001144950.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.21

Publications

2 publications found

Variant links:

Genes affected

SSC5D (HGNC:26641): (scavenger receptor cysteine rich family member with 5 domains) Predicted to enable fibronectin binding activity; laminin binding activity; and scavenger receptor activity. Predicted to be involved in defense response; detection of bacterial lipoprotein; and negative regulation of interleukin-8 production. Predicted to act upstream of or within regulation of interleukin-8 production. Predicted to be located in collagen-containing extracellular matrix. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SSC5D links:

ENSG00000300360 (HGNC:):

ENSG00000300360 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030222237).

BP6

Variant 19-55518207-C-G is Benign according to our data. Variant chr19-55518207-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 403489.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSC5D	NM_001144950.2 link	c.3931C>G	p.Pro1311Ala	missense_variant	Exon 14 of 14	ENST00000389623.11	NP_001138422.1	A1L4H1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSC5D	ENST00000389623.11 link	c.3931C>G	p.Pro1311Ala	missense_variant	Exon 14 of 14	1	NM_001144950.2	ENSP00000374274.4		A1L4H1-1
ENSG00000300360	ENST00000771167.1 link	n.231+2565G>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

180

AN:

114066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00693

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000669

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000507

Gnomad OTH

AF:

0.00323

GnomAD2 exomes

AF:

0.000361

AC:

AN:

143996

AF XY:

0.000287

show subpopulations

Gnomad AFR exome

AF:

0.00678

Gnomad AMR exome

AF:

0.000355

Gnomad ASJ exome

AF:

0.000389

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.000730

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000401

AC:

527

AN:

1314004

Hom.:

Cov.:

AF XY:

0.000358

AC XY:

232

AN XY:

647656

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0146

AC:

399

AN:

27236

American (AMR)

AF:

0.000969

AC:

AN:

29916

Ashkenazi Jewish (ASJ)

AF:

0.000487

AC:

AN:

22570

East Asian (EAS)

AF:

0.00

AC:

AN:

30070

South Asian (SAS)

AF:

0.0000526

AC:

AN:

75986

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44522

Middle Eastern (MID)

AF:

0.000928

AC:

AN:

5390

European-Non Finnish (NFE)

AF:

0.0000283

AC:

AN:

1024990

Other (OTH)

AF:

0.000938

AC:

AN:

53324

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.298

Heterozygous variant carriers

119

159

199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00159

AC:

182

AN:

114120

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

AN XY:

55406

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00700

AC:

160

AN:

22854

American (AMR)

AF:

0.00111

AC:

AN:

10836

Ashkenazi Jewish (ASJ)

AF:

0.000669

AC:

AN:

2990

East Asian (EAS)

AF:

0.00

AC:

AN:

3296

South Asian (SAS)

AF:

0.00

AC:

AN:

4258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.0000507

AC:

AN:

59140

Other (OTH)

AF:

0.00318

AC:

AN:

1572

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.310

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0358

Hom.:

ExAC

AF:

0.00521

AC:

128

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.1

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.013

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.065

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.6

PhyloP100

-1.2

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.33

REVEL

Benign

0.082

Sift

Benign

0.041

Sift4G

Benign

0.51

Polyphen

0.60

Vest4

0.14

MVP

0.048

MPC

0.014

ClinPred

0.0033

GERP RS

2.5

Varity_R

0.024

gMVP

0.065

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over