Variant 2-240888496-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001085437.3(MAB21L4):c.1047G>C(p.Gln349His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,605,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

MAB21L4
NM_001085437.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0550

Variant links:

Genes affected

MAB21L4 (HGNC:26216): (mab-21 like 4)

MAB21L4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15739599).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAB21L4	NM_001085437.3 linkuse as main transcript	c.1047G>C	p.Gln349His	missense_variant	4/5	ENST00000388934.5	NP_001078906.3
MAB21L4	NM_001282921.2 linkuse as main transcript	c.600G>C	p.Gln200His	missense_variant	4/5		NP_001269850.2
MAB21L4	NM_024861.4 linkuse as main transcript	c.543G>C	p.Gln181His	missense_variant	4/5		NP_079137.4
MAB21L4	XM_011511877.2 linkuse as main transcript	c.1047G>C	p.Gln349His	missense_variant	5/6		XP_011510179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAB21L4	ENST00000388934.5 linkuse as main transcript	c.1047G>C	p.Gln349His	missense_variant	4/5	2	NM_001085437.3	ENSP00000373586	P1	Q08AI8-1
MAB21L4	ENST00000307486.12 linkuse as main transcript	c.600G>C	p.Gln200His	missense_variant	4/5	1		ENSP00000302779		Q08AI8-2
MAB21L4	ENST00000402775.6 linkuse as main transcript	c.543G>C	p.Gln181His	missense_variant	4/5	2		ENSP00000385338		Q08AI8-3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000442

AC:

AN:

226394

Hom.:

AF XY:

0.00000797

AC XY:

AN XY:

125430

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000179

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1453286

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

723060

show subpopulations

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:

0.0000198

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000595

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000832

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.1047G>C (p.Q349H) alteration is located in exon 4 (coding exon 4) of the C2orf54 gene. This alteration results from a G to C substitution at nucleotide position 1047, causing the glutamine (Q) at amino acid position 349 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

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

.;.;T

Eigen

Benign

-0.054

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.51

T;T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.69

N;N;N

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.034

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.031

D;D;D

Polyphen

0.83

P;.;P

Vest4

0.17

MutPred

0.23

.;.;Gain of disorder (P = 0.1047);

MVP

0.14

MPC

0.068

ClinPred

0.63

GERP RS

3.4

Varity_R

0.23

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over