3-8985623-G-A

Variant summary

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

The NM_014850.4(SRGAP3):​c.3196C>T​(p.His1066Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SRGAP3
NM_014850.4 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.19
Variant links:
Genes affected
SRGAP3 (HGNC:19744): (SLIT-ROBO Rho GTPase activating protein 3) Predicted to enable GTPase activator activity. Predicted to be involved in negative regulation of cell migration. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.14918312).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRGAP3NM_014850.4 linkuse as main transcriptc.3196C>T p.His1066Tyr missense_variant 22/22 ENST00000383836.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRGAP3ENST00000383836.8 linkuse as main transcriptc.3196C>T p.His1066Tyr missense_variant 22/221 NM_014850.4 P1O43295-1
SRGAP3ENST00000360413.7 linkuse as main transcriptc.3124C>T p.His1042Tyr missense_variant 22/221 O43295-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1443754
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
718306
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:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 24, 2022The c.3196C>T (p.H1066Y) alteration is located in exon 22 (coding exon 22) of the SRGAP3 gene. This alteration results from a C to T substitution at nucleotide position 3196, causing the histidine (H) at amino acid position 1066 to be replaced by a tyrosine (Y). 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
0.14
BayesDel_addAF
Benign
-0.067
T
BayesDel_noAF
Benign
-0.33
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;.
Eigen
Benign
0.044
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-0.51
N;N
REVEL
Benign
0.13
Sift
Benign
0.045
D;D
Sift4G
Benign
0.19
T;T
Polyphen
0.17
B;B
Vest4
0.36
MutPred
0.24
Gain of phosphorylation at H1066 (P = 0.0154);.;
MVP
0.068
MPC
1.6
ClinPred
0.95
D
GERP RS
5.1
Varity_R
0.14
gMVP
0.31

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

LitVar

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

Other links and lift over

dbSNP: rs1482076914; hg19: chr3-9027307; API