15-48835003-C-A

Variant names:

• chr15-48835003-C-A
• NM_203349.4:c.1503G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203349.4(SHC4):​c.1503G>T​(p.Gln501His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SHC4 NM_203349.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292

Genes affected

SHC4 (HGNC:16743): (SHC adaptor protein 4) Predicted to enable receptor tyrosine kinase binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within several processes, including apoptotic process; positive regulation of cell population proliferation; and stem cell differentiation. Predicted to be located in postsynaptic membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21938825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.1503G>T	p.Gln501His	missense_variant	Exon 11 of 12	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.954G>T	p.Gln318His	missense_variant	Exon 11 of 12		XP_005254432.1
SHC4	XM_047432492.1	c.645G>T	p.Gln215His	missense_variant	Exon 8 of 9		XP_047288448.1
SHC4	XM_047432493.1	c.645G>T	p.Gln215His	missense_variant	Exon 9 of 10		XP_047288449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.1503G>T	p.Gln501His	missense_variant	Exon 11 of 12	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459470 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725918

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: 0.0000188

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;T
Eigen	Benign	-0.029
Eigen_PC	Benign	0.0051
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.0	M;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.047
Sift	Uncertain	0.023	D;D;D
Sift4G	Benign	0.12	T;T;T
Polyphen		0.17	B;D;.
Vest4		0.27
MutPred		0.097		Gain of glycosylation at T499 (P = 0.0615);.;.;
MVP		0.63
MPC		0.21
ClinPred		0.67	D
GERP RS		2.7
Varity_R		0.11
gMVP		0.34

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: chr15-49127200;