14-73722735-T-C

Variant names:

• chr14-73722735-T-C
• rs770875882
• NM_001367710.1:c.2687A>G

Variant summary

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

The NM_001367710.1(MIDEAS):​c.2687A>G​(p.Glu896Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIDEAS NM_001367710.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98

Genes affected

MIDEAS (HGNC:19853): (mitotic deacetylase associated SANT domain protein) Predicted to enable transcription corepressor activity. Predicted to be involved in histone deacetylation; negative regulation of transcription, DNA-templated; and regulation of transcription by RNA polymerase II. Located in nucleoplasm. [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=0.2957397).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIDEAS	NM_001367710.1	c.2687A>G	p.Glu896Gly	missense_variant	Exon 10 of 13	ENST00000423556.7	NP_001354639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIDEAS	ENST00000423556.7	c.2687A>G	p.Glu896Gly	missense_variant	Exon 10 of 13	2	NM_001367710.1	ENSP00000407767.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251472 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135910

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2687A>G (p.E896G) alteration is located in exon 10 (coding exon 9) of the ELMSAN1 gene. This alteration results from a A to G substitution at nucleotide position 2687, causing the glutamic acid (E) at amino acid position 896 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.033	T;T;.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.75	.;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L;L;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.024	D;D;D;.
Polyphen		0.99	D;D;.;.
Vest4		0.49
MutPred		0.20		Loss of solvent accessibility (P = 0.0477);Loss of solvent accessibility (P = 0.0477);Loss of solvent accessibility (P = 0.0477);Loss of solvent accessibility (P = 0.0477);
MVP		0.15
MPC		0.68
ClinPred		0.88	D
GERP RS		5.5
Varity_R		0.33
gMVP		0.21

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: rs770875882; hg19: chr14-74189438;