20-1537194-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.982
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
SIRPDNM_178460.3 linkc.538G>T p.Val180Phe missense_variant Exon 3 of 4 ENST00000381623.4 NP_848555.2 Q9H106

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIRPDENST00000381623.4 linkc.538G>T p.Val180Phe missense_variant Exon 3 of 4 1 NM_178460.3 ENSP00000371036.3 Q9H106
SIRPDENST00000381621.5 linkc.541G>T p.Val181Phe missense_variant Exon 3 of 4 3 ENSP00000371034.1 Q5TFQ5
SIRPDENST00000429387.5 linkc.184G>T p.Val62Phe missense_variant Exon 2 of 3 3 ENSP00000410072.1 H0Y747
ENSG00000242324ENST00000453770.1 linkn.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
show subpopulations
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs143061754; hg19: chr20-1517840; API