4-3249286-G-A

Position:

chr4-3249286-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001042690.2(MSANTD1):c.64G>A(p.Gly22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000853 in 1,524,022 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

MSANTD1
NM_001042690.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.541

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024773031).

BP6

Variant 4-3249286-G-A is Benign according to our data. Variant chr4-3249286-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3296196.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSANTD1	NM_001042690.2 linkuse as main transcript	c.64G>A	p.Gly22Ser	missense_variant	1/3	ENST00000438480.7	NP_001036155.1	Q6ZTZ1
MSANTD1	NM_001330620.2 linkuse as main transcript	c.25G>A	p.Gly9Ser	missense_variant	4/6		NP_001317549.1	D6R9L8
MSANTD1	XM_011513467.4 linkuse as main transcript	c.64G>A	p.Gly22Ser	missense_variant	1/2		XP_011511769.1
MSANTD1	XM_047415655.1 linkuse as main transcript	c.25G>A	p.Gly9Ser	missense_variant	2/3		XP_047271611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MSANTD1	ENST00000438480.7 linkuse as main transcript	c.64G>A	p.Gly22Ser	missense_variant	1/3	5	NM_001042690.2	ENSP00000411584.2	Q6ZTZ1
MSANTD1	ENST00000507492.5 linkuse as main transcript	c.25G>A	p.Gly9Ser	missense_variant	4/6	1		ENSP00000423547.1	D6R9L8
MSANTD1	ENST00000510580.1 linkuse as main transcript	c.64G>A	p.Gly22Ser	missense_variant	1/4	5		ENSP00000420966.1	D6RDG6
MSANTD1	ENST00000505599.5 linkuse as main transcript	n.64G>A		non_coding_transcript_exon_variant	1/6	2		ENSP00000425405.1	D6RD98

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152192

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000904

AC:

AN:

132752

Hom.:

AF XY:

0.0000418

AC XY:

AN XY:

71700

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000129

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000491

Gnomad FIN exome

AF:

0.000155

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000882

AC:

121

AN:

1371830

Hom.:

Cov.:

AF XY:

0.0000758

AC XY:

AN XY:

672888

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000147

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000567

Gnomad4 SAS exome

AF:

0.0000130

Gnomad4 FIN exome

AF:

0.000132

Gnomad4 NFE exome

AF:

0.0000978

Gnomad4 OTH exome

AF:

0.0000529

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000245

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.14

DANN

Benign

0.84

DEOGEN2

Benign

0.00026

.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.49

T;T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.025

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.66

.;N;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.090

N;N;N

REVEL

Benign

0.041

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.96

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.13

MVP

0.014

MPC

0.32

ClinPred

0.035

GERP RS

-2.8

Varity_R

0.036

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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