chr11-124799893-G-C

Position:

• chr11-124799893-G-C

Variant summary

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

The ENST00000374979.8(MSANTD2):​c.488C>G​(p.Ser163Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000699 in 1,431,528 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MSANTD2 ENST00000374979.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.16

Genes affected

MSANTD2 (HGNC:26266): (Myb/SANT DNA binding domain containing 2)

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
MSANTD2	NM_001308027.2	c.488C>G	p.Ser163Cys	missense_variant	1/4	ENST00000374979.8	NP_001294956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSANTD2	ENST00000374979.8	c.488C>G	p.Ser163Cys	missense_variant	1/4	1	NM_001308027.2	ENSP00000364118	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1431528 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 712014

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000260

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Sep 07, 2022

The c.488C>G (p.S163C) alteration is located in exon 1 (coding exon 1) of the MSANTD2 gene. This alteration results from a C to G substitution at nucleotide position 488, causing the serine (S) at amino acid position 163 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	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Pathogenic	0.57	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.2	L;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.27
Sift	Benign	0.12	T;D;D
Sift4G	Uncertain	0.028	D;D;T
Polyphen		1.0	D;D;.
Vest4		0.38
MutPred		0.32		Loss of phosphorylation at S163 (P = 0.0134);Loss of phosphorylation at S163 (P = 0.0134);Loss of phosphorylation at S163 (P = 0.0134);
MVP		0.37
MPC		0.75
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.53
gMVP		0.86

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

Other links and lift over

dbSNP: rs1221599605; hg19: chr11-124669789;