rs770251464

Variant names:

• chr10-80538491-C-T
• rs770251464
• NM_001388272.1:c.160C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-80538491-C-T
• chr10-80538491-C-A

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.160C>T​(p.Leu54Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000042 in 1,430,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (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: 0.00200
• 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=0.07680932).

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.160C>T	p.Leu54Phe	missense	Exon 1 of 8	NP_001375201.1	A0A2R8Y5Q0
	SH2D4B	NM_207372.2		c.160C>T	p.Leu54Phe	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.160C>T	p.Leu54Phe	missense	Exon 1 of 8	ENSP00000494732.1	A0A2R8Y5Q0
	SH2D4B	ENST00000339284.6	TSL:2	c.160C>T	p.Leu54Phe	missense	Exon 1 of 7	ENSP00000345295.2	Q5SQS7-2
	TSPAN14-AS1	ENST00000837327.1		n.200-1097G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

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

GnomAD2 exomes AF: 0.0000391 AC: 3 AN: 76748 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000168

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000287

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000391 AC: 5 AN: 1278004 Hom.: 0 Cov.: 30 AF XY: 0.00000160 AC XY: 1 AN XY: 623282

African (AFR) AF: 0.00 AC: 0 AN: 27874

American (AMR) AF: 0.0000625 AC: 1 AN: 15994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18414

East Asian (EAS) AF: 0.0000600 AC: 2 AN: 33326

South Asian (SAS) AF: 0.00 AC: 0 AN: 58310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1022640

Other (OTH) AF: 0.0000383 AC: 2 AN: 52180

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

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

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

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: 0.0000340

ExAC AF: 0.0000278 AC: 3

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	0.077
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.1
DANN	Uncertain	0.98
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.0020
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.048
Sift	Benign	0.11	T
Sift4G	Benign	0.28	T
Polyphen		0.43	B
Vest4		0.091
MutPred		0.28		Gain of methylation at K58 (P = 0.1)
MVP		0.22
MPC		0.17
ClinPred		0.020	T
GERP RS		-0.66
gMVP		0.050
Mutation Taster		=96/4	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: rs770251464; hg19: chr10-82298247;