rs1021537180

Variant names:

• chr10-80538392-G-A
• rs1021537180
• NM_001388272.1:c.61G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-80538392-G-A
• chr10-80538392-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001388272.1(SH2D4B):​c.61G>A​(p.Asp21Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,446,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: SH2D4B NM_001388272.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.05
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2490915).

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.61G>A	p.Asp21Asn	missense	Exon 1 of 8	NP_001375201.1	A0A2R8Y5Q0
	SH2D4B	NM_207372.2		c.61G>A	p.Asp21Asn	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.61G>A	p.Asp21Asn	missense	Exon 1 of 8	ENSP00000494732.1	A0A2R8Y5Q0
	SH2D4B	ENST00000339284.6	TSL:2	c.61G>A	p.Asp21Asn	missense	Exon 1 of 7	ENSP00000345295.2	Q5SQS7-2
	TSPAN14-AS1	ENST00000837327.1		n.200-998C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000386 AC: 5 AN: 1294720 Hom.: 0 Cov.: 30 AF XY: 0.00000316 AC XY: 2 AN XY: 633560

African (AFR) AF: 0.0000722 AC: 2 AN: 27706

American (AMR) AF: 0.00 AC: 0 AN: 18758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20252

East Asian (EAS) AF: 0.0000311 AC: 1 AN: 32124

South Asian (SAS) AF: 0.0000159 AC: 1 AN: 62880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1028766

Other (OTH) AF: 0.0000189 AC: 1 AN: 52936

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000482 AC: 2 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

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	0.28
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	-0.0085
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		8.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.081
Sift	Benign	0.033	D
Sift4G	Benign	0.11	T
Polyphen		0.035	B
Vest4		0.24
MutPred		0.37		Gain of MoRF binding (P = 0.062)
MVP		0.51
MPC		0.15
ClinPred		0.94	D
GERP RS		4.5
PromoterAI		0.011	Neutral
gMVP		0.13
Mutation Taster		=85/15	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

dbSNP: rs1021537180; hg19: chr10-82298148; COSMIC: COSV57899205; COSMIC: COSV57899205;