4-3249310-G-A

Position:

• chr4-3249310-G-A

Variant summary

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

The NM_001042690.2(MSANTD1):​c.88G>A​(p.Gly30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000461 in 1,540,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: MSANTD1 NM_001042690.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.709

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]

ACMG classification

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	c.88G>A	p.Gly30Ser	missense_variant	1/3	ENST00000438480.7	NP_001036155.1
MSANTD1	NM_001330620.2	c.49G>A	p.Gly17Ser	missense_variant	4/6		NP_001317549.1
MSANTD1	XM_011513467.4	c.88G>A	p.Gly30Ser	missense_variant	1/2		XP_011511769.1
MSANTD1	XM_047415655.1	c.49G>A	p.Gly17Ser	missense_variant	2/3		XP_047271611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSANTD1	ENST00000438480.7	c.88G>A	p.Gly30Ser	missense_variant	1/3	5	NM_001042690.2	ENSP00000411584.2
MSANTD1	ENST00000507492.5	c.49G>A	p.Gly17Ser	missense_variant	4/6	1		ENSP00000423547.1
MSANTD1	ENST00000510580.1	c.88G>A	p.Gly30Ser	missense_variant	1/4	5		ENSP00000420966.1
MSANTD1	ENST00000505599.5	n.88G>A		non_coding_transcript_exon_variant	1/6	2		ENSP00000425405.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152188 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000122 AC: 18 AN: 147448 Hom.: 0 AF XY: 0.000126 AC XY: 10 AN XY: 79384

Gnomad AFR exome AF: 0.000137

Gnomad AMR exome AF: 0.000244

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000185

Gnomad SAS exome AF: 0.000177

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000728

Gnomad OTH exome AF: 0.000235

GnomAD4 exome AF: 0.0000476 AC: 66 AN: 1387870 Hom.: 0 Cov.: 31 AF XY: 0.0000498 AC XY: 34 AN XY: 682266

Gnomad4 AFR exome AF: 0.0000635

Gnomad4 AMR exome AF: 0.000141

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000253

Gnomad4 SAS exome AF: 0.000114

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000364

Gnomad4 OTH exome AF: 0.0000349

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152306 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74482

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000388 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.88G>A (p.G30S) alteration is located in exon 1 (coding exon 1) of the MSANTD1 gene. This alteration results from a G to A substitution at nucleotide position 88, causing the glycine (G) at amino acid position 30 to be replaced by a serine (S). 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	0.070
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.7
DANN	Benign	0.95
DEOGEN2	Benign	0.00081	.;T;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.0075	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.67	.;N;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.83	N;N;N
REVEL	Benign	0.051
Sift	Benign	0.69	T;T;T
Sift4G	Benign	0.87	T;T;T
Polyphen		0.017	.;B;.
Vest4		0.10
MutPred		0.13		.;Gain of glycosylation at Y31 (P = 0.002);Gain of glycosylation at Y31 (P = 0.002);
MVP		0.014
MPC		0.34
ClinPred		0.0051	T
GERP RS		-1.1
Varity_R		0.033
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: 21

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

Publications

LitVar

Other links and lift over

dbSNP: rs555136963; hg19: chr4-3251037;