Genetic Variant NM_001144950.2:c.3930C>A (chr19-55518206-C-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_001144950.2(SSC5D):c.3930C>A(p.Thr1310Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T1310T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SSC5D
NM_001144950.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0140

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP7

Synonymous conserved (PhyloP=0.014 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144950.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSC5D	NM_001144950.2	MANE Select	c.3930C>A	p.Thr1310Thr	synonymous	Exon 14 of 14	NP_001138422.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSC5D	ENST00000389623.11	TSL:1 MANE Select	c.3930C>A	p.Thr1310Thr	synonymous	Exon 14 of 14	ENSP00000374274.4
	ENSG00000300360	ENST00000771167.1		n.231+2566G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000904

AC:

AN:

110626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000330

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1314798

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

648048

African (AFR)

AF:

0.00

AC:

AN:

27428

American (AMR)

AF:

0.00

AC:

AN:

29914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22586

East Asian (EAS)

AF:

0.00

AC:

AN:

30030

South Asian (SAS)

AF:

0.00

AC:

AN:

76030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5396

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1025532

Other (OTH)

AF:

0.00

AC:

AN:

53350

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000904

AC:

AN:

110626

Hom.:

Cov.:

AF XY:

0.0000186

AC XY:

AN XY:

53714

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

22050

American (AMR)

AF:

0.00

AC:

AN:

10136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2888

East Asian (EAS)

AF:

0.000330

AC:

AN:

3030

South Asian (SAS)

AF:

0.00

AC:

AN:

4312

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7844

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

57770

Other (OTH)

AF:

0.00

AC:

AN:

1518

⚠️ 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: 0.325

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.75

(source)

DANN

Benign

0.43

PhyloP100

0.014

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over