1-116133159-T-C

Position:

• chr1-116133159-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152367.3(MAB21L3):​c.883T>C​(p.Tyr295His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAB21L3 NM_152367.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2647192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAB21L3	NM_152367.3	c.883T>C	p.Tyr295His	missense_variant	8/8	ENST00000369500.4	NP_689580.2
MAB21L3	XM_047444823.1	c.883T>C	p.Tyr295His	missense_variant	7/7		XP_047300779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAB21L3	ENST00000369500.4	c.883T>C	p.Tyr295His	missense_variant	8/8	2	NM_152367.3	ENSP00000358512	P1
MAB21L3	ENST00000683341.1	c.883T>C	p.Tyr295His	missense_variant	7/7			ENSP00000508049	P1
MAB21L3	ENST00000684484.1	c.883T>C	p.Tyr295His	missense_variant	7/7			ENSP00000506754	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

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

Feb 12, 2024

The c.883T>C (p.Y295H) alteration is located in exon 7 (coding exon 6) of the MAB21L3 gene. This alteration results from a T to C substitution at nucleotide position 883, causing the tyrosine (Y) at amino acid position 295 to be replaced by a histidine (H). 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	0.25
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.24
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.070
Sift	Benign	0.84	T
Sift4G	Benign	0.14	T
Polyphen		0.76	P
Vest4		0.30
MutPred		0.54		Gain of methylation at K294 (P = 0.0592);
MVP		0.34
MPC		0.098
ClinPred		0.35	T
GERP RS		3.0
Varity_R		0.048
gMVP		0.54

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: chr1-116675780;