rs370018372

Variant names:

• chr20-1537268-G-A
• rs370018372
• NM_178460.3:c.464C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-1537268-G-A
• chr20-1537268-G-C
• chr20-1537268-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178460.3(SIRPD):​c.464C>T​(p.Ala155Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,860 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (1 hom.)
• Consequence: SIRPD NM_178460.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

Genes affected

SIRPD (HGNC:16248): (signal regulatory protein delta) Predicted to be located in extracellular region. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000242324 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0566864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPD	NM_178460.3	c.464C>T	p.Ala155Val	missense_variant	Exon 3 of 4	ENST00000381623.4	NP_848555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRPD	ENST00000381623.4	c.464C>T	p.Ala155Val	missense_variant	Exon 3 of 4	1	NM_178460.3	ENSP00000371036.3
SIRPD	ENST00000381621.5	c.467C>T	p.Ala156Val	missense_variant	Exon 3 of 4	3		ENSP00000371034.1
SIRPD	ENST00000429387.5	c.110C>T	p.Ala37Val	missense_variant	Exon 2 of 3	3		ENSP00000410072.1
ENSG00000242324	ENST00000453770.1	n.803-3474C>T		intron_variant	Intron 3 of 5	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251206 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135728

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 SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461860 Hom.: 1 Cov.: 30 AF XY: 0.00000825 AC XY: 6 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	.;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.017
Sift	Benign	0.076	T;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.20	.;B
Vest4		0.15
MutPred		0.34		.;Loss of catalytic residue at A155 (P = 0.0658);
MVP		0.040
MPC		0.24
ClinPred		0.054	T
GERP RS		-0.37
Varity_R		0.049
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs370018372; hg19: chr20-1517914;