chr10-80603665-A-T

Position:

• chr10-80603665-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001388272.1(SH2D4B):​c.730A>T​(p.Ile244Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SH2D4B NM_001388272.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.41

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29882842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D4B	NM_001388272.1	c.730A>T	p.Ile244Phe	missense_variant	5/8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2	c.730A>T	p.Ile244Phe	missense_variant	5/7		NP_997255.2
SH2D4B	NM_001145719.1	c.583A>T	p.Ile195Phe	missense_variant	5/7		NP_001139191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D4B	ENST00000646907.2	c.730A>T	p.Ile244Phe	missense_variant	5/8		NM_001388272.1	ENSP00000494732	P1
SH2D4B	ENST00000339284.6	c.730A>T	p.Ile244Phe	missense_variant	5/7	2		ENSP00000345295
SH2D4B	ENST00000313455.5	c.583A>T	p.Ile195Phe	missense_variant	5/7	2		ENSP00000314242

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457230 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 724474

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: 0.0000235

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.730A>T (p.I244F) alteration is located in exon 5 (coding exon 5) of the SH2D4B gene. This alteration results from a A to T substitution at nucleotide position 730, causing the isoleucine (I) at amino acid position 244 to be replaced by a phenylalanine (F). 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
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.7	N;.;N
REVEL	Benign	0.095
Sift	Uncertain	0.022	D;.;D
Sift4G	Benign	0.067	T;.;D
Polyphen		1.0	D;.;D
Vest4		0.66
MutPred		0.22		Loss of methylation at K246 (P = 0.0823);Loss of methylation at K246 (P = 0.0823);.;
MVP		0.72
MPC		0.69
ClinPred		0.95	D
GERP RS		4.9
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-82363421;