19-4283132-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020209.4(SHD):​c.482C>T​(p.Ser161Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SHD
NM_020209.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0810
Variant links:
Genes affected
SHD (HGNC:30633): (Src homology 2 domain containing transforming protein D) Predicted to enable phosphotyrosine residue binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14640716).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SHDNM_020209.4 linkc.482C>T p.Ser161Phe missense_variant Exon 3 of 6 ENST00000543264.7 NP_064594.3 Q96IW2
SHDNM_001372011.1 linkc.482C>T p.Ser161Phe missense_variant Exon 4 of 7 NP_001358940.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SHDENST00000543264.7 linkc.482C>T p.Ser161Phe missense_variant Exon 3 of 6 1 NM_020209.4 ENSP00000446058.1 Q96IW2
SHDENST00000599689.1 linkc.482C>T p.Ser161Phe missense_variant Exon 3 of 5 5 ENSP00000470181.1 M0QYZ4
SHDENST00000593383.1 linkn.50C>T non_coding_transcript_exon_variant Exon 1 of 4 3 ENSP00000472139.1 M0R1V9

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250860
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135642
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461856
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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.:
31
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.482C>T (p.S161F) alteration is located in exon 3 (coding exon 3) of the SHD gene. This alteration results from a C to T substitution at nucleotide position 482, causing the serine (S) at amino acid position 161 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T;.
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.079
N
LIST_S2
Benign
0.48
T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.90
L;.
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.8
N;.
REVEL
Benign
0.059
Sift
Benign
0.048
D;.
Sift4G
Benign
0.18
T;T
Polyphen
0.58
P;.
Vest4
0.16
MutPred
0.16
Loss of phosphorylation at S161 (P = 0.0122);Loss of phosphorylation at S161 (P = 0.0122);
MVP
0.52
MPC
0.17
ClinPred
0.10
T
GERP RS
-0.51
Varity_R
0.093
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs1269049964; hg19: chr19-4283129; COSMIC: COSV73378694; COSMIC: COSV73378694; API