rs561939776

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-1551760-C-A
• chr20-1551760-C-G
• chr20-1551760-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178460.3(SIRPD):​c.352G>T​(p.Val118Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V118M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SIRPD NM_178460.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.923

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPD	NM_178460.3	c.352G>T	p.Val118Leu	missense_variant	Exon 2 of 4	ENST00000381623.4	NP_848555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRPD	ENST00000381623.4	c.352G>T	p.Val118Leu	missense_variant	Exon 2 of 4	1	NM_178460.3	ENSP00000371036.3
ENSG00000260861	ENST00000564763.1	c.*204G>T		downstream_gene_variant		4		ENSP00000457944.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461798 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727198

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	7.6
DANN	Benign	0.93
DEOGEN2	Benign	0.26	.;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.50	N
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.0074	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Pathogenic	2.9	.;M
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.28	.;B
Vest4		0.44
MutPred		0.71		Gain of catalytic residue at V118 (P = 0.0054);Gain of catalytic residue at V118 (P = 0.0054);
MVP		0.42
MPC		0.20
ClinPred		0.81	D
GERP RS		1.6
Varity_R		0.28
gMVP		0.28

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-1532406;