5-50441081-A-G

Variant names:

• chr5-50441081-A-G
• NM_198449.3:c.71T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_198449.3(EMB):​c.71T>C​(p.Leu24Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EMB NM_198449.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40
• Publications: 0 publications found

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]

ENSG00000298748 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198449.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMB	NM_198449.3	MANE Select	c.71T>C	p.Leu24Pro	missense	Exon 1 of 9	NP_940851.1	Q6PCB8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMB	ENST00000303221.10	TSL:1 MANE Select	c.71T>C	p.Leu24Pro	missense	Exon 1 of 9	ENSP00000302289.5	Q6PCB8-1
	EMB	ENST00000872546.1		c.71T>C	p.Leu24Pro	missense	Exon 1 of 8	ENSP00000542605.1
	EMB	ENST00000508934.5	TSL:5	c.71T>C	p.Leu24Pro	missense	Exon 1 of 9	ENSP00000425215.1	D6RDX7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1366790 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 674066

African (AFR) AF: 0.00 AC: 0 AN: 29122

American (AMR) AF: 0.00 AC: 0 AN: 33784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24542

East Asian (EAS) AF: 0.00 AC: 0 AN: 33692

South Asian (SAS) AF: 0.00 AC: 0 AN: 76278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4330

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067804

Other (OTH) AF: 0.00 AC: 0 AN: 56844

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.30	T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.4
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.67
MutPred		0.45		Gain of sheet (P = 0.0016)
MVP		0.58
MPC		0.17
ClinPred		0.38	T
GERP RS		2.9
PromoterAI		-0.044	Neutral
Varity_R		0.49
gMVP		0.72
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr5-49736915;