20-1537194-C-A

Variant names:

• chr20-1537194-C-A
• rs143061754
• NM_178460.3:c.538G>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.538G>T​(p.Val180Phe) 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 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V180I) has been classified as Likely benign.

• 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: -0.982

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=0.04218644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPD	NM_178460.3	c.538G>T	p.Val180Phe	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.538G>T	p.Val180Phe	missense_variant	Exon 3 of 4	1	NM_178460.3	ENSP00000371036.3
SIRPD	ENST00000381621.5	c.541G>T	p.Val181Phe	missense_variant	Exon 3 of 4	3		ENSP00000371034.1
SIRPD	ENST00000429387.5	c.184G>T	p.Val62Phe	missense_variant	Exon 2 of 3	3		ENSP00000410072.1
ENSG00000242324	ENST00000453770.1	n.803-3400G>T		intron_variant	Intron 3 of 5	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727224

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.51
DANN	Benign	0.70
DEOGEN2	Benign	0.0061	.;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.39	T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.0	N;N
REVEL	Benign	0.087
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.048	D;T
Polyphen		0.054	.;B
Vest4		0.16
MutPred		0.18		.;Gain of disorder (P = 0.1334);
MVP		0.014
MPC		0.054
ClinPred		0.13	T
GERP RS		-2.6
Varity_R		0.052
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs143061754; hg19: chr20-1517840;