rs751054150

Variant names:

• chr9-129012244-C-A
• NM_020145.4:c.616G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-129012244-C-A
• chr9-129012244-C-T

Variant summary

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

The NM_020145.4(SH3GLB2):​c.616G>T​(p.Ala206Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000876 in 1,141,706 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. A206T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: SH3GLB2 NM_020145.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.90

Genes affected

SH3GLB2 (HGNC:10834): (SH3 domain containing GRB2 like, endophilin B2) Enables identical protein binding activity. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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
SH3GLB2	NM_020145.4	c.616G>T	p.Ala206Ser	missense_variant	Exon 6 of 11	ENST00000372564.8	NP_064530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3GLB2	ENST00000372564.8	c.616G>T	p.Ala206Ser	missense_variant	Exon 6 of 11	1	NM_020145.4	ENSP00000361645.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.76e-7 AC: 1 AN: 1141706 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 544134

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: 0.0000259

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T;T;.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	.;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.23	N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.25	T;T;D;T
Sift4G	Benign	0.43	T;T;T;T
Polyphen		0.66	P;P;P;.
Vest4		0.60
MutPred		0.60		Gain of disorder (P = 0.0473);Gain of disorder (P = 0.0473);.;Gain of disorder (P = 0.0473);
MVP		0.36
MPC		0.91
ClinPred		0.83	D
GERP RS		5.8
Varity_R		0.11
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-131774523;