chr20-1551760-C-T

Variant names:

• chr20-1551760-C-T
• rs561939776
• NM_178460.3:c.352G>A

Variant summary

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

The NM_178460.3(SIRPD):​c.352G>A​(p.Val118Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: SIRPD NM_178460.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.923
• Publications: 3 publications found

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]

ENSG00000260861 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16565707).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178460.3. 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
	SIRPD	NM_178460.3	MANE Select	c.352G>A	p.Val118Met	missense	Exon 2 of 4	NP_848555.2	Q9H106
	SIRPD	NM_001410802.1		c.352G>A	p.Val118Met	missense	Exon 2 of 4	NP_001397731.1	Q5TFQ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRPD	ENST00000381623.4	TSL:1 MANE Select	c.352G>A	p.Val118Met	missense	Exon 2 of 4	ENSP00000371036.3	Q9H106
	SIRPD	ENST00000381621.5	TSL:3	c.352G>A	p.Val118Met	missense	Exon 2 of 4	ENSP00000371034.1	Q5TFQ5
	ENSG00000260861	ENST00000566961.2	TSL:3	c.369+5821G>A		intron	N/A	ENSP00000457551.2	H3BUA5

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000716 AC: 18 AN: 251246 AF XY: 0.0000589

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000322 AC: 47 AN: 1461798 Hom.: 0 Cov.: 30 AF XY: 0.0000316 AC XY: 23 AN XY: 727198

African (AFR) AF: 0.0000896 AC: 3 AN: 33470

American (AMR) AF: 0.000224 AC: 10 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111944

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74452

African (AFR) AF: 0.0000481 AC: 2 AN: 41556

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68008

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

Alfa AF: 0.000127 Hom.: 0

Bravo AF: 0.0000907

ExAC AF: 0.0000494 AC: 6

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	0.27
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		0.92
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.15
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.019	D
Polyphen		0.96	P
Vest4		0.30
MVP		0.44
MPC		0.23
ClinPred		0.26	T
GERP RS		1.6
PromoterAI		-0.018	Neutral
Varity_R		0.096
gMVP		0.26
Mutation Taster		=98/2	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: rs561939776; hg19: chr20-1532406; COSMIC: COSV101064901; COSMIC: COSV101064901;