NM_001388272.1:c.314G>C

Variant names:

• chr10-80570283-G-C
• NM_001388272.1:c.314G>C

Variant summary

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

The NM_001388272.1(SH2D4B):​c.314G>C​(p.Arg105Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,344 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. R105Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SH2D4B NM_001388272.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.85

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 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
SH2D4B	NM_001388272.1	c.314G>C	p.Arg105Pro	missense_variant	Exon 2 of 8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2	c.314G>C	p.Arg105Pro	missense_variant	Exon 2 of 7		NP_997255.2
SH2D4B	NM_001145719.1	c.167G>C	p.Arg56Pro	missense_variant	Exon 2 of 7		NP_001139191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2D4B	ENST00000646907.2	c.314G>C	p.Arg105Pro	missense_variant	Exon 2 of 8		NM_001388272.1	ENSP00000494732.1
SH2D4B	ENST00000339284.6	c.314G>C	p.Arg105Pro	missense_variant	Exon 2 of 7	2		ENSP00000345295.2
SH2D4B	ENST00000313455.5	c.167G>C	p.Arg56Pro	missense_variant	Exon 2 of 7	2		ENSP00000314242.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461344 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726958

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: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	32
DANN	Uncertain	1.0
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.5	D;.;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0050	D;.;D
Sift4G	Uncertain	0.0060	D;.;D
Polyphen		1.0	D;.;D
Vest4		0.80
MutPred		0.31		Loss of MoRF binding (P = 0.0225);Loss of MoRF binding (P = 0.0225);.;
MVP		0.59
MPC		0.79
ClinPred		0.99	D
GERP RS		5.6
gMVP		0.87

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-82330039;