Genetic Variant NM_001144950.2:c.3931C>T (chr19-55518207-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001144950.2(SSC5D):c.3931C>T(p.Pro1311Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000761 in 1,314,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1311A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

SSC5D
NM_001144950.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.085893184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSC5D	NM_001144950.2 link	c.3931C>T	p.Pro1311Ser	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>T	p.Pro1311Ser	missense_variant	Exon 14 of 14	1	NM_001144950.2	ENSP00000374274.4		A1L4H1-1
ENSG00000300360	ENST00000771167.1 link	n.231+2565G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000694

AC:

AN:

143996

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000443

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.61e-7

AC:

AN:

1314340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

647794

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

27472

American (AMR)

AF:

0.0000334

AC:

AN:

29920

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22580

East Asian (EAS)

AF:

0.00

AC:

AN:

30070

South Asian (SAS)

AF:

0.00

AC:

AN:

75990

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5394

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1025016

Other (OTH)

AF:

0.00

AC:

AN:

53376

⚠️ 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: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.3

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0098

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.040

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.041

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.4

PhyloP100

-1.2

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.060

REVEL

Benign

0.056

Sift

Benign

0.034

Sift4G

Benign

0.068

Polyphen

0.60

Vest4

0.071

MutPred

0.26

Gain of phosphorylation at P1311 (P = 0.0103);

MVP

0.048

MPC

0.014

ClinPred

0.080

GERP RS

2.5

Varity_R

0.025

gMVP

0.11

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over