11-106009796-A-C

Variant names:

• chr11-106009796-A-C
• rs1859631960
• NM_032424.3:c.777T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032424.3(MSANTD4):​c.777T>G​(p.Ile259Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,888 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: MSANTD4 NM_032424.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.70

Genes affected

MSANTD4 (HGNC:29383): (Myb/SANT DNA binding domain containing 4 with coiled-coils) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.057216734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSANTD4	NM_032424.3	c.777T>G	p.Ile259Met	missense_variant	Exon 3 of 3	ENST00000301919.9	NP_115800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSANTD4	ENST00000301919.9	c.777T>G	p.Ile259Met	missense_variant	Exon 3 of 3	1	NM_032424.3	ENSP00000304713.4
MSANTD4	ENST00000530788.1	c.*188T>G		downstream_gene_variant		1		ENSP00000435125.1
MSANTD4	ENST00000529805.1	n.-48T>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727246

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: 0.00000989

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 11, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.777T>G (p.I259M) alteration is located in exon 3 (coding exon 2) of the MSANTD4 gene. This alteration results from a T to G substitution at nucleotide position 777, causing the isoleucine (I) at amino acid position 259 to be replaced by a methionine (M). 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	0.074
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.13
DANN	Benign	0.89
DEOGEN2	Benign	0.054	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.11	N
REVEL	Uncertain	0.33
Sift	Benign	0.053	T
Sift4G	Benign	0.14	T
Polyphen		0.79	P
Vest4		0.18
MutPred		0.15		Loss of catalytic residue at L264 (P = 0.0473);
MVP		0.10
MPC		0.49
ClinPred		0.36	T
GERP RS		-9.3
Varity_R		0.036
gMVP		0.059

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: rs1859631960; hg19: chr11-105880523;