4-3255779-G-T

Position:

• chr4-3255779-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042690.2(MSANTD1):​c.651G>T​(p.Lys217Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MSANTD1 NM_001042690.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11485499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSANTD1	NM_001042690.2	c.651G>T	p.Lys217Asn	missense_variant	3/3	ENST00000438480.7	NP_001036155.1
MSANTD1	NM_001330620.2	c.612G>T	p.Lys204Asn	missense_variant	6/6		NP_001317549.1
MSANTD1	XM_011513467.4	c.375G>T	p.Lys125Asn	missense_variant	2/2		XP_011511769.1
MSANTD1	XM_047415655.1	c.336G>T	p.Lys112Asn	missense_variant	3/3		XP_047271611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSANTD1	ENST00000438480.7	c.651G>T	p.Lys217Asn	missense_variant	3/3	5	NM_001042690.2	ENSP00000411584.2
MSANTD1	ENST00000507492.5	c.612G>T	p.Lys204Asn	missense_variant	6/6	1		ENSP00000423547.1
MSANTD1	ENST00000510580.1	c.651G>T	p.Lys217Asn	missense_variant	3/4	5		ENSP00000420966.1
MSANTD1	ENST00000505599.5	n.651G>T		non_coding_transcript_exon_variant	3/6	2		ENSP00000425405.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394722 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 688024

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Mar 27, 2023

The c.651G>T (p.K217N) alteration is located in exon 3 (coding exon 3) of the MSANTD1 gene. This alteration results from a G to T substitution at nucleotide position 651, causing the lysine (K) at amino acid position 217 to be replaced by an asparagine (N). 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	0.62
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	.;T;.
Eigen	Benign	0.045
Eigen_PC	Benign	0.074
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D;D;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	.;L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.037
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.55	.;P;.
Vest4		0.14
MutPred		0.15		.;Gain of glycosylation at S212 (P = 0.0162);Gain of glycosylation at S212 (P = 0.0162);
MVP		0.048
MPC		0.65
ClinPred		0.86	D
GERP RS		3.0
Varity_R		0.19
gMVP		0.45

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: rs1226824345; hg19: chr4-3257506;