rs778514407

chr19-55518207-C-Gchr19-55518207-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 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 [Benign]. Clinvar id is 403489.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSC5D	NM_001144950.2	c.3931C>G	p.Pro1311Ala	missense_variant	14/14	ENST00000389623.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSC5D	ENST00000389623.11	c.3931C>G	p.Pro1311Ala	missense_variant	14/14	1	NM_001144950.2	P2

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 180 AN: 114066 Hom.: 0 Cov.: 22

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

GnomAD3 exomes AF: 0.000361 AC: 52 AN: 143996 Hom.: 0 AF XY: 0.000287 AC XY: 22 AN XY: 76708

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 SAS 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.: 0 Cov.: 74 AF XY: 0.000358 AC XY: 232 AN XY: 647656

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.000969

Gnomad4 ASJ exome AF: 0.000487

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000526

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000283

Gnomad4 OTH exome AF: 0.000938

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00159 AC: 182 AN: 114120 Hom.: 0 Cov.: 22 AF XY: 0.00170 AC XY: 94 AN XY: 55406

Gnomad4 AFR AF: 0.00700

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.000669

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000507

Gnomad4 OTH AF: 0.00318

Alfa AF: 0.0358 Hom.: 0

ExAC AF: 0.00521 AC: 128

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	1.1
Dann	Benign	0.85
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.065	N
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.082
Sift	Benign	0.041	D
Sift4G	Benign	0.51	T
Polyphen		0.60	P
Vest4		0.14
MVP		0.048
MPC		0.014
ClinPred		0.0033	T
GERP RS		2.5
Varity_R		0.024
gMVP		0.065

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

LitVar

Other links and lift over

dbSNP: rs778514407; hg19: chr19-56029574;