Variant 4-3253442-C-T 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.556C>T(p.Arg186Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000633 in 1,578,974 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

MSANTD1
NM_001042690.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0580

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=0.06051886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSANTD1	NM_001042690.2 linkuse as main transcript	c.556C>T	p.Arg186Cys	missense_variant	2/3	ENST00000438480.7	NP_001036155.1	Q6ZTZ1
MSANTD1	NM_001330620.2 linkuse as main transcript	c.517C>T	p.Arg173Cys	missense_variant	5/6		NP_001317549.1	D6R9L8
MSANTD1	XM_011513467.4 linkuse as main transcript	c.321-2283C>T		intron_variant			XP_011511769.1
MSANTD1	XM_047415655.1 linkuse as main transcript	c.282-2283C>T		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.556C>T	p.Arg186Cys	missense_variant	2/3	5	NM_001042690.2	ENSP00000411584.2	Q6ZTZ1
MSANTD1	ENST00000507492.5 linkuse as main transcript	c.517C>T	p.Arg173Cys	missense_variant	5/6	1		ENSP00000423547.1	D6R9L8
MSANTD1	ENST00000510580.1 linkuse as main transcript	c.556C>T	p.Arg186Cys	missense_variant	2/4	5		ENSP00000420966.1	D6RDG6
MSANTD1	ENST00000505599.5 linkuse as main transcript	n.556C>T		non_coding_transcript_exon_variant	2/6	2		ENSP00000425405.1	D6RD98

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000255

AC:

AN:

235572

Hom.:

AF XY:

0.0000314

AC XY:

AN XY:

127368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000131

Gnomad ASJ exome

AF:

0.000103

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:

0.00000561

AC:

AN:

1426756

Hom.:

Cov.:

AF XY:

0.00000709

AC XY:

AN XY:

705430

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000966

Gnomad4 ASJ exome

AF:

0.0000390

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

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 30, 2024

The c.556C>T (p.R186C) alteration is located in exon 2 (coding exon 2) of the MSANTD1 gene. This alteration results from a C to T substitution at nucleotide position 556, causing the arginine (R) at amino acid position 186 to be replaced by a cysteine (C). 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

0.087

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0055

.;T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.0092

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.0075

MetaRNN

Benign

0.061

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

.;L;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.071

Sift

Benign

0.071

T;T;D

Sift4G

Benign

0.18

T;T;T

Polyphen

0.99

.;D;.

Vest4

0.32

MutPred

0.22

.;Gain of glycosylation at S187 (P = 4e-04);Gain of glycosylation at S187 (P = 4e-04);

MVP

0.072

MPC

0.72

ClinPred

0.14

GERP RS

-1.2

Varity_R

0.11

gMVP

0.39

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