11-106010541-T-G

Position:

• chr11-106010541-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000301919.9(MSANTD4):​c.377A>C​(p.Gln126Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MSANTD4 ENST00000301919.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.93

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.264676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSANTD4	NM_032424.3	c.377A>C	p.Gln126Pro	missense_variant	2/3	ENST00000301919.9	NP_115800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSANTD4	ENST00000301919.9	c.377A>C	p.Gln126Pro	missense_variant	2/3	1	NM_032424.3	ENSP00000304713.4
MSANTD4	ENST00000530788.1	c.377A>C	p.Gln126Pro	missense_variant	2/3	1		ENSP00000435125.1
MSANTD4	ENST00000534458.1	c.*44A>C		downstream_gene_variant		4		ENSP00000432245.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 04, 2022

The c.377A>C (p.Q126P) alteration is located in exon 2 (coding exon 1) of the MSANTD4 gene. This alteration results from a A to C substitution at nucleotide position 377, causing the glutamine (Q) at amino acid position 126 to be replaced by a proline (P). 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	0.12
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.053	T;.;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.0	L;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	N;.;N
REVEL	Benign	0.11
Sift	Benign	0.19	T;.;T
Sift4G	Benign	0.066	T;D;.
Polyphen		0.33	B;.;.
Vest4		0.43
MutPred		0.39		Gain of loop (P = 0.0013);.;Gain of loop (P = 0.0013);
MVP		0.31
MPC		0.38
ClinPred		0.56	D
GERP RS		5.9
Varity_R		0.24
gMVP		0.22

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: rs1251391854; hg19: chr11-105881268;