19-55489377-C-T

Variant names:

• chr19-55489377-C-T
• rs1000094188
• NM_001144950.2:c.76C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144950.2(SSC5D):​c.76C>T​(p.Pro26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000739 in 1,474,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000078 (0 hom.)
• Consequence: SSC5D NM_001144950.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.206
• Publications: 0 publications found

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

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=0.24237797).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSC5D	NM_001144950.2	MANE Select	c.76C>T	p.Pro26Ser	missense	Exon 3 of 14	NP_001138422.1	A1L4H1-1
	SSC5D	NM_001195267.2		c.76C>T	p.Pro26Ser	missense	Exon 3 of 13	NP_001182196.1	A1L4H1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSC5D	ENST00000389623.11	TSL:1 MANE Select	c.76C>T	p.Pro26Ser	missense	Exon 3 of 14	ENSP00000374274.4	A1L4H1-1
	SSC5D	ENST00000587166.5	TSL:1	c.76C>T	p.Pro26Ser	missense	Exon 3 of 13	ENSP00000467252.1	A1L4H1-2
	SSC5D	ENST00000594321.5	TSL:4	c.76C>T	p.Pro26Ser	missense	Exon 3 of 3	ENSP00000470226.1	M0QZ17

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152244 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000715 AC: 5 AN: 69884 AF XY: 0.0000264

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000774

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000121

Gnomad OTH exome AF: 0.000465

GnomAD4 exome AF: 0.0000779 AC: 103 AN: 1322376 Hom.: 0 Cov.: 31 AF XY: 0.0000554 AC XY: 36 AN XY: 649442

African (AFR) AF: 0.00 AC: 0 AN: 26556

American (AMR) AF: 0.0000438 AC: 1 AN: 22854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20242

East Asian (EAS) AF: 0.00 AC: 0 AN: 32690

South Asian (SAS) AF: 0.00 AC: 0 AN: 67786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4256

European-Non Finnish (NFE) AF: 0.0000950 AC: 100 AN: 1052494

Other (OTH) AF: 0.0000365 AC: 2 AN: 54822

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74378

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.029
Eigen_PC	Benign	-0.081
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.47	N
PhyloP100		0.21
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.10
Sift	Benign	0.27	T
Sift4G	Benign	0.86	T
Polyphen		0.99	D
Vest4		0.23
MutPred		0.32		Loss of sheet (P = 0.0817)
MVP		0.47
MPC		0.11
ClinPred		0.14	T
GERP RS		4.0
Varity_R		0.068
gMVP		0.27
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1000094188; hg19: chr19-56000744;