chr10-80538367-C-A

Variant names:

• chr10-80538367-C-A
• NM_001388272.1:c.36C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001388272.1(SH2D4B):​c.36C>A​(p.Asp12Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SH2D4B NM_001388272.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.660
• Publications: 0 publications found

Genes affected

SH2D4B (HGNC:31440): (SH2 domain containing 4B) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TSPAN14-AS1 (HGNC:55833): (TSPAN14 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388272.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D4B	NM_001388272.1	MANE Select	c.36C>A	p.Asp12Glu	missense	Exon 1 of 8	NP_001375201.1	A0A2R8Y5Q0
	SH2D4B	NM_207372.2		c.36C>A	p.Asp12Glu	missense	Exon 1 of 7	NP_997255.2	Q5SQS7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D4B	ENST00000646907.2	MANE Select	c.36C>A	p.Asp12Glu	missense	Exon 1 of 8	ENSP00000494732.1	A0A2R8Y5Q0
	SH2D4B	ENST00000339284.6	TSL:2	c.36C>A	p.Asp12Glu	missense	Exon 1 of 7	ENSP00000345295.2	Q5SQS7-2
	TSPAN14-AS1	ENST00000837327.1		n.200-973G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1251268 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 606790

African (AFR) AF: 0.00 AC: 0 AN: 26290

American (AMR) AF: 0.00 AC: 0 AN: 14984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18004

East Asian (EAS) AF: 0.00 AC: 0 AN: 30536

South Asian (SAS) AF: 0.00 AC: 0 AN: 55382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4412

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1005862

Other (OTH) AF: 0.00 AC: 0 AN: 51022

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Uncertain	1.0
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0098	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.66
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.23
Sift	Benign	0.083	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.35
MutPred		0.61		Loss of phosphorylation at Y10 (P = 0.1774)
MVP		0.58
MPC		0.54
ClinPred		0.98	D
GERP RS		3.7
PromoterAI		-0.016	Neutral
gMVP		0.23
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

hg19: chr10-82298123; COSMIC: COSV57898471; COSMIC: COSV57898471;