chr1-116127630-G-A

Position:

• chr1-116127630-G-A

Variant summary

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

The NM_152367.3(MAB21L3):​c.646G>A​(p.Val216Met) variant causes a missense change. 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)
• Consequence: MAB21L3 NM_152367.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71

Genes affected

MAB21L3 (HGNC:26787): (mab-21 like 3)

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/exons	MANE	Protein	UniProt
MAB21L3	NM_152367.3	c.646G>A	p.Val216Met	missense_variant	6/8	ENST00000369500.4	NP_689580.2
MAB21L3	XM_047444823.1	c.646G>A	p.Val216Met	missense_variant	5/7		XP_047300779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAB21L3	ENST00000369500.4	c.646G>A	p.Val216Met	missense_variant	6/8	2	NM_152367.3	ENSP00000358512.3
MAB21L3	ENST00000683341.1	c.646G>A	p.Val216Met	missense_variant	5/7			ENSP00000508049.1
MAB21L3	ENST00000684484.1	c.646G>A	p.Val216Met	missense_variant	5/7			ENSP00000506754.1
MAB21L3	ENST00000464946.1	n.484G>A		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.646G>A (p.V216M) alteration is located in exon 5 (coding exon 4) of the MAB21L3 gene. This alteration results from a G to A substitution at nucleotide position 646, causing the valine (V) at amino acid position 216 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0082	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.61
MutPred		0.52		Gain of catalytic residue at V216 (P = 0.0037);
MVP		0.69
MPC		0.37
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.26
gMVP		0.36

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: chr1-116670251;