5-50410915-C-A

Variant names:

• chr5-50410915-C-A
• NM_198449.3:c.434G>T

Variant summary

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

The NM_198449.3(EMB):​c.434G>T​(p.Arg145Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/25 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. R145Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EMB NM_198449.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

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 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
EMB	NM_198449.3	c.434G>T	p.Arg145Leu	missense_variant	Exon 4 of 9	ENST00000303221.10	NP_940851.1
EMB	XM_011543146.3	c.284G>T	p.Arg95Leu	missense_variant	Exon 5 of 10		XP_011541448.1
EMB	XM_047416702.1	c.284G>T	p.Arg95Leu	missense_variant	Exon 4 of 9		XP_047272658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMB	ENST00000303221.10	c.434G>T	p.Arg145Leu	missense_variant	Exon 4 of 9	1	NM_198449.3	ENSP00000302289.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1453136 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 722732

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: 0.00

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
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.018	T;T;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.094	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.024
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.14	B;B;.
Vest4		0.25
MutPred		0.39		Loss of disorder (P = 0.0398);.;.;
MVP		0.21
MPC		0.14
ClinPred		0.12	T
GERP RS		-1.4
Varity_R		0.051
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: -3
DS_DL_spliceai		0.44		Position offset: -38

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: chr5-49706749;