rs367637105

Variant names:

• chr14-73721298-G-A
• rs367637105
• NM_001367710.1:c.2936C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-73721298-G-A
• chr14-73721298-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001367710.1(MIDEAS):​c.2936C>T​(p.Ser979Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000918 in 1,612,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000092 (0 hom.)
• Consequence: MIDEAS NM_001367710.1 missense, splice_region
• Scores: Splicing: ADA: 0.05887
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.80
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07630035).

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.2936C>T	p.Ser979Leu	missense splice_region	Exon 11 of 13	NP_001354639.1	A0A1C7CYX1
	MIDEAS	NM_001394972.1		c.2936C>T	p.Ser979Leu	missense splice_region	Exon 11 of 13	NP_001381901.1	A0A1C7CYX1
	MIDEAS	NM_001043318.3		c.2936C>T	p.Ser979Leu	missense splice_region	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.2936C>T	p.Ser979Leu	missense splice_region	Exon 11 of 13	ENSP00000407767.2	A0A1C7CYX1
	MIDEAS	ENST00000286523.9	TSL:1	c.2936C>T	p.Ser979Leu	missense splice_region	Exon 11 of 12	ENSP00000286523.5	Q6PJG2
	MIDEAS	ENST00000394071.6	TSL:1	c.2936C>T	p.Ser979Leu	missense splice_region	Exon 11 of 12	ENSP00000377634.2	Q6PJG2

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152096 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000686 AC: 17 AN: 247752 AF XY: 0.0000819

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000719

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000925 AC: 135 AN: 1459972 Hom.: 0 Cov.: 31 AF XY: 0.0000867 AC XY: 63 AN XY: 726452

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000962 AC: 107 AN: 1111976

Other (OTH) AF: 0.0000497 AC: 3 AN: 60378

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152096 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74274

African (AFR) AF: 0.00 AC: 0 AN: 41392

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000710 Hom.: 0

Bravo AF: 0.0000604

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.086
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.046
Sift	Benign	0.054	T
Sift4G	Benign	0.51	T
Polyphen		0.20	B
Vest4		0.30
MVP		0.12
MPC		0.35
ClinPred		0.073	T
GERP RS		4.0
Varity_R		0.048
gMVP		0.17
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.059
dbscSNV1_RF	Benign	0.21
SpliceAI score (max)		0.010		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: rs367637105; hg19: chr14-74188001; COSMIC: COSV99678913; COSMIC: COSV99678913;