14-73721461-T-C

Variant names:

• chr14-73721461-T-C
• rs60635070
• NM_001367710.1:c.2773A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001367710.1(MIDEAS):​c.2773A>G​(p.Ser925Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,614,058 control chromosomes in the GnomAD database, including 1,973 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S925C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.071 (924 hom., cov: 32)
  • Exomes 𝑓: 0.019 (1049 hom.)
• Consequence: MIDEAS NM_001367710.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.150
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.316504E-4).
• BP6: Variant 14-73721461-T-C is Benign according to our data. Variant chr14-73721461-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3126374.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367710.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIDEAS	NM_001367710.1	MANE Select	c.2773A>G	p.Ser925Gly	missense	Exon 11 of 13	NP_001354639.1	A0A1C7CYX1
	MIDEAS	NM_001394972.1		c.2773A>G	p.Ser925Gly	missense	Exon 11 of 13	NP_001381901.1	A0A1C7CYX1
	MIDEAS	NM_001043318.3		c.2773A>G	p.Ser925Gly	missense	Exon 11 of 12	NP_001036783.1	Q6PJG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIDEAS	ENST00000423556.7	TSL:2 MANE Select	c.2773A>G	p.Ser925Gly	missense	Exon 11 of 13	ENSP00000407767.2	A0A1C7CYX1
	MIDEAS	ENST00000286523.9	TSL:1	c.2773A>G	p.Ser925Gly	missense	Exon 11 of 12	ENSP00000286523.5	Q6PJG2
	MIDEAS	ENST00000394071.6	TSL:1	c.2773A>G	p.Ser925Gly	missense	Exon 11 of 12	ENSP00000377634.2	Q6PJG2

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 10745 AN: 152070 Hom.: 922 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0627

GnomAD2 exomes AF: 0.0292 AC: 7269 AN: 249030 AF XY: 0.0267

Gnomad AFR exome AF: 0.208

Gnomad AMR exome AF: 0.0323

Gnomad ASJ exome AF: 0.0197

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.00342

Gnomad NFE exome AF: 0.0159

Gnomad OTH exome AF: 0.0307

GnomAD4 exome AF: 0.0192 AC: 28049 AN: 1461870 Hom.: 1049 Cov.: 31 AF XY: 0.0189 AC XY: 13744 AN XY: 727236

African (AFR) AF: 0.214 AC: 7148 AN: 33480

American (AMR) AF: 0.0338 AC: 1512 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0192 AC: 501 AN: 26136

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.0172 AC: 1480 AN: 86258

European-Finnish (FIN) AF: 0.00331 AC: 177 AN: 53414

Middle Eastern (MID) AF: 0.0704 AC: 406 AN: 5768

European-Non Finnish (NFE) AF: 0.0135 AC: 15010 AN: 1111998

Other (OTH) AF: 0.0299 AC: 1808 AN: 60396

GnomAD4 genome AF: 0.0707 AC: 10759 AN: 152188 Hom.: 924 Cov.: 32 AF XY: 0.0688 AC XY: 5119 AN XY: 74436

African (AFR) AF: 0.203 AC: 8418 AN: 41452

American (AMR) AF: 0.0582 AC: 891 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0184 AC: 89 AN: 4826

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10618

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0159 AC: 1081 AN: 68026

Other (OTH) AF: 0.0620 AC: 131 AN: 2112

Alfa AF: 0.0351 Hom.: 460

Bravo AF: 0.0815

TwinsUK AF: 0.0132 AC: 49

ALSPAC AF: 0.0135 AC: 52

ESP6500AA AF: 0.204 AC: 898

ESP6500EA AF: 0.0159 AC: 137

ExAC AF: 0.0317 AC: 3845

Asia WGS AF: 0.0230 AC: 80 AN: 3478

EpiCase AF: 0.0229

EpiControl AF: 0.0211

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.00093	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.15
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.026
Sift	Benign	0.20	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.047
MPC		0.35
ClinPred		0.0036	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.22
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs60635070; hg19: chr14-74188164; COSMIC: COSV54092275; COSMIC: COSV54092275;