Variant chr4-3253410-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001042690.2(MSANTD1):c.524A>G(p.Gln175Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,599,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MSANTD1
NM_001042690.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

MSANTD1 (HGNC:33741): (Myb/SANT DNA binding domain containing 1) Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to be active in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

MSANTD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024726152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSANTD1	NM_001042690.2 linkuse as main transcript	c.524A>G	p.Gln175Arg	missense_variant	2/3	ENST00000438480.7	NP_001036155.1	Q6ZTZ1
MSANTD1	NM_001330620.2 linkuse as main transcript	c.485A>G	p.Gln162Arg	missense_variant	5/6		NP_001317549.1	D6R9L8
MSANTD1	XM_011513467.4 linkuse as main transcript	c.321-2315A>G		intron_variant			XP_011511769.1
MSANTD1	XM_047415655.1 linkuse as main transcript	c.282-2315A>G		intron_variant			XP_047271611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MSANTD1	ENST00000438480.7 linkuse as main transcript	c.524A>G	p.Gln175Arg	missense_variant	2/3	5	NM_001042690.2	ENSP00000411584.2	Q6ZTZ1
MSANTD1	ENST00000507492.5 linkuse as main transcript	c.485A>G	p.Gln162Arg	missense_variant	5/6	1		ENSP00000423547.1	D6R9L8
MSANTD1	ENST00000510580.1 linkuse as main transcript	c.524A>G	p.Gln175Arg	missense_variant	2/4	5		ENSP00000420966.1	D6RDG6
MSANTD1	ENST00000505599.5 linkuse as main transcript	n.524A>G		non_coding_transcript_exon_variant	2/6	2		ENSP00000425405.1	D6RD98

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000455

AC:

AN:

241762

Hom.:

AF XY:

0.0000230

AC XY:

AN XY:

130664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000630

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1447526

Hom.:

Cov.:

AF XY:

0.00000974

AC XY:

AN XY:

718652

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000411

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000494

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

Oct 16, 2023

The c.524A>G (p.Q175R) alteration is located in exon 2 (coding exon 2) of the MSANTD1 gene. This alteration results from a A to G substitution at nucleotide position 524, causing the glutamine (Q) at amino acid position 175 to be replaced by an arginine (R). 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

0.068

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0038

.;T;.

Eigen

Benign

0.020

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.025

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

.;L;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.92

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.36

.;B;.

Vest4

0.21

MVP

0.030

MPC

0.35

ClinPred

0.11

GERP RS

5.3

Varity_R

0.20

gMVP

0.37

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

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