NM_001144950.2:c.269G>A

Variant names:

• chr19-55489570-G-A
• rs756136708
• NM_001144950.2:c.269G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001144950.2(SSC5D):​c.269G>A​(p.Arg90Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000402 in 1,511,240 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R90W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (1 hom.)
• Consequence: SSC5D NM_001144950.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.548
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12210718).

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.269G>A	p.Arg90Gln	missense	Exon 3 of 14	NP_001138422.1	A1L4H1-1
	SSC5D	NM_001195267.2		c.269G>A	p.Arg90Gln	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.269G>A	p.Arg90Gln	missense	Exon 3 of 14	ENSP00000374274.4	A1L4H1-1
	SSC5D	ENST00000587166.5	TSL:1	c.269G>A	p.Arg90Gln	missense	Exon 3 of 13	ENSP00000467252.1	A1L4H1-2
	SSC5D	ENST00000594321.5	TSL:4	c.269G>A	p.Arg90Gln	missense splice_region	Exon 3 of 3	ENSP00000470226.1	M0QZ17

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000179 AC: 20 AN: 111590 AF XY: 0.000214

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000356

Gnomad OTH exome AF: 0.000584

GnomAD4 exome AF: 0.000425 AC: 578 AN: 1358954 Hom.: 1 Cov.: 32 AF XY: 0.000441 AC XY: 295 AN XY: 669034

African (AFR) AF: 0.0000978 AC: 3 AN: 30690

American (AMR) AF: 0.0000316 AC: 1 AN: 31688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23352

East Asian (EAS) AF: 0.00 AC: 0 AN: 35432

South Asian (SAS) AF: 0.0000396 AC: 3 AN: 75732

European-Finnish (FIN) AF: 0.0000603 AC: 2 AN: 33172

Middle Eastern (MID) AF: 0.000373 AC: 2 AN: 5364

European-Non Finnish (NFE) AF: 0.000514 AC: 548 AN: 1066878

Other (OTH) AF: 0.000335 AC: 19 AN: 56646

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74464

African (AFR) AF: 0.0000962 AC: 4 AN: 41560

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 67996

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.0000855 Hom.: 0

Bravo AF: 0.000208

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ExAC AF: 0.000112 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	Benign	0.085
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.55
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.081
Sift	Benign	0.088	T
Sift4G	Benign	0.23	T
Polyphen		0.91	P
Vest4		0.15
MVP		0.10
MPC		0.021
ClinPred		0.068	T
GERP RS		2.9
Varity_R		0.094
gMVP		0.27
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs756136708; hg19: chr19-56000937;