rs776043166

Variant names:

• chr19-4280292-C-G
• NM_020209.4:c.229C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-4280292-C-G
• chr19-4280292-C-T

Variant summary

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

The NM_020209.4(SHD):​c.229C>G​(p.Arg77Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,704 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. R77W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SHD NM_020209.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64

Genes affected

SHD (HGNC:30633): (Src homology 2 domain containing transforming protein D) Predicted to enable phosphotyrosine residue binding activity. [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
SHD	NM_020209.4	c.229C>G	p.Arg77Gly	missense_variant	Exon 1 of 6	ENST00000543264.7	NP_064594.3
SHD	NM_001372011.1	c.229C>G	p.Arg77Gly	missense_variant	Exon 2 of 7		NP_001358940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHD	ENST00000543264.7	c.229C>G	p.Arg77Gly	missense_variant	Exon 1 of 6	1	NM_020209.4	ENSP00000446058.1
SHD	ENST00000599689.1	c.229C>G	p.Arg77Gly	missense_variant	Exon 1 of 5	5		ENSP00000470181.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458704 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725516

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: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.5	D;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.56
MutPred		0.37		Loss of MoRF binding (P = 0.0076);Loss of MoRF binding (P = 0.0076);
MVP		0.89
MPC		0.75
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.76
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: chr19-4280289;