1-116128239-A-G

Position:

• chr1-116128239-A-G

Variant summary

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

The NM_152367.3(MAB21L3):​c.755A>G​(p.Asp252Gly) 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: 7.05

Genes affected

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

MAB21L3 (HGNC:):

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.755A>G	p.Asp252Gly	missense_variant	7/8	ENST00000369500.4	NP_689580.2
MAB21L3	XM_047444823.1	c.755A>G	p.Asp252Gly	missense_variant	6/7		XP_047300779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAB21L3	ENST00000369500.4	c.755A>G	p.Asp252Gly	missense_variant	7/8	2	NM_152367.3	ENSP00000358512.3
MAB21L3	ENST00000683341.1	c.755A>G	p.Asp252Gly	missense_variant	6/7			ENSP00000508049.1
MAB21L3	ENST00000684484.1	c.755A>G	p.Asp252Gly	missense_variant	6/7			ENSP00000506754.1
MAB21L3	ENST00000464946.1	n.593A>G		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Apr 26, 2023

The c.755A>G (p.D252G) alteration is located in exon 6 (coding exon 5) of the MAB21L3 gene. This alteration results from a A to G substitution at nucleotide position 755, causing the aspartic acid (D) at amino acid position 252 to be replaced by a glycine (G). 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	0.28
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.17
Sift	Benign	0.048	D
Sift4G	Uncertain	0.046	D
Polyphen		0.54	P
Vest4		0.82
MutPred		0.45		Gain of catalytic residue at D252 (P = 0.0254);
MVP		0.55
MPC		0.22
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.23
gMVP		0.49

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: chr1-116670860;