5-50441124-C-T

Variant names:

• chr5-50441124-C-T
• NM_198449.3:c.28G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198449.3(EMB):​c.28G>A​(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,357,732 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. 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. A10S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: EMB NM_198449.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

Genes affected

EMB (HGNC:30465): (embigin) This gene encodes a transmembrane glycoprotein that is a member of the immunoglobulin superfamily. The encoded protein may be involved in cell growth and development by mediating interactions between the cell and extracellular matrix. A pseudogene of this gene is found on chromosome 1. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046845913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMB	NM_198449.3	c.28G>A	p.Ala10Thr	missense_variant	Exon 1 of 9	ENST00000303221.10	NP_940851.1
EMB	XM_011543146.3	c.-39+1828G>A		intron_variant	Intron 2 of 9		XP_011541448.1
EMB	XM_047416702.1	c.-39+218G>A		intron_variant	Intron 1 of 8		XP_047272658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMB	ENST00000303221.10	c.28G>A	p.Ala10Thr	missense_variant	Exon 1 of 9	1	NM_198449.3	ENSP00000302289.5
EMB	ENST00000508934.5	c.28G>A	p.Ala10Thr	missense_variant	Exon 1 of 9	5		ENSP00000425215.1
EMB	ENST00000506190.1	n.92+1828G>A		intron_variant	Intron 2 of 6	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1357732 Hom.: 0 Cov.: 31 AF XY: 0.00000149 AC XY: 1 AN XY: 669372

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: 9.39e-7

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	Benign	0.18
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.4
DANN	Benign	0.93
DEOGEN2	Benign	0.048	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.34	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.047	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.011
Sift	Benign	0.24	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.022	B;B
Vest4		0.093
MutPred		0.19		Gain of phosphorylation at A10 (P = 0.0113);Gain of phosphorylation at A10 (P = 0.0113);
MVP		0.36
MPC		0.093
ClinPred		0.069	T
GERP RS		-1.6
Varity_R		0.051
gMVP		0.41

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: chr5-49736958;