19-55489419-C-A

Variant names:

• chr19-55489419-C-A
• rs771562073
• NM_001144950.2:c.118C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001144950.2(SSC5D):​c.118C>A​(p.Arg40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,337,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R40H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SSC5D NM_001144950.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3321504).

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.118C>A	p.Arg40Ser	missense	Exon 3 of 14	NP_001138422.1	A1L4H1-1
	SSC5D	NM_001195267.2		c.118C>A	p.Arg40Ser	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.118C>A	p.Arg40Ser	missense	Exon 3 of 14	ENSP00000374274.4	A1L4H1-1
	SSC5D	ENST00000587166.5	TSL:1	c.118C>A	p.Arg40Ser	missense	Exon 3 of 13	ENSP00000467252.1	A1L4H1-2
	SSC5D	ENST00000594321.5	TSL:4	c.118C>A	p.Arg40Ser	missense	Exon 3 of 3	ENSP00000470226.1	M0QZ17

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1337136 Hom.: 0 Cov.: 31 AF XY: 0.00000152 AC XY: 1 AN XY: 658430

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

African (AFR) AF: 0.00 AC: 0 AN: 27212

American (AMR) AF: 0.00 AC: 0 AN: 25986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21478

East Asian (EAS) AF: 0.00 AC: 0 AN: 33014

South Asian (SAS) AF: 0.00 AC: 0 AN: 71252

European-Finnish (FIN) AF: 0.0000256 AC: 1 AN: 39104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4786

European-Non Finnish (NFE) AF: 9.44e-7 AC: 1 AN: 1058798

Other (OTH) AF: 0.00 AC: 0 AN: 55506

⚠️ 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.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.28	N
PhyloP100		-0.38
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.20
Sift	Benign	0.26	T
Sift4G	Benign	1.0	T
Polyphen		0.14	B
Vest4		0.38
MutPred		0.66		Loss of sheet (P = 0.0817)
MVP		0.099
MPC		0.11
ClinPred		0.79	D
GERP RS		4.2
Varity_R		0.16
gMVP		0.32
Mutation Taster		=68/32	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: rs771562073; hg19: chr19-56000786;