Variant 4-3253421-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001042690.2(MSANTD1):c.535G>A(p.Glu179Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000314 in 1,594,312 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MSANTD1
NM_001042690.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.87

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 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
MSANTD1	NM_001042690.2 linkuse as main transcript	c.535G>A	p.Glu179Lys	missense_variant	2/3	ENST00000438480.7	NP_001036155.1	Q6ZTZ1
MSANTD1	NM_001330620.2 linkuse as main transcript	c.496G>A	p.Glu166Lys	missense_variant	5/6		NP_001317549.1	D6R9L8
MSANTD1	XM_011513467.4 linkuse as main transcript	c.321-2304G>A		intron_variant			XP_011511769.1
MSANTD1	XM_047415655.1 linkuse as main transcript	c.282-2304G>A		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.535G>A	p.Glu179Lys	missense_variant	2/3	5	NM_001042690.2	ENSP00000411584.2	Q6ZTZ1
MSANTD1	ENST00000507492.5 linkuse as main transcript	c.496G>A	p.Glu166Lys	missense_variant	5/6	1		ENSP00000423547.1	D6R9L8
MSANTD1	ENST00000510580.1 linkuse as main transcript	c.535G>A	p.Glu179Lys	missense_variant	2/4	5		ENSP00000420966.1	D6RDG6
MSANTD1	ENST00000505599.5 linkuse as main transcript	n.535G>A		non_coding_transcript_exon_variant	2/6	2		ENSP00000425405.1	D6RD98

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241438

Hom.:

AF XY:

0.00000766

AC XY:

AN XY:

130508

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:

0.00000897

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1442112

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

715364

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:

0.00000273

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Apr 20, 2023

The c.535G>A (p.E179K) alteration is located in exon 2 (coding exon 2) of the MSANTD1 gene. This alteration results from a G to A substitution at nucleotide position 535, causing the glutamic acid (E) at amino acid position 179 to be replaced by a lysine (K). 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

0.12

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.011

.;T;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.49

T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.1

.;M;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.69

MutPred

0.26

.;Gain of ubiquitination at E179 (P = 0.0048);Gain of ubiquitination at E179 (P = 0.0048);

MVP

0.11

MPC

1.1

ClinPred

0.95

GERP RS

5.3

Varity_R

0.46

gMVP

0.64

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