NM_001393769.1:c.16C>A

Variant names:

• chr3-151086942-C-A
• rs532455340
• NM_001393769.1:c.16C>A

Variant summary

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

The NM_001393769.1(MED12L):​c.16C>A​(p.Leu6Ile) 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. 14/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MED12L NM_001393769.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60

Genes affected

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

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=0.045645088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED12L	NM_001393769.1	c.16C>A	p.Leu6Ile	missense_variant	Exon 2 of 45	ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED12L	ENST00000687756.1	c.16C>A	p.Leu6Ile	missense_variant	Exon 2 of 45		NM_001393769.1	ENSP00000508695.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1451222 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 721182

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.0082	.;.;T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.035
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.57	T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.046	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N;N;N;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.31	N;N;N;N
REVEL	Benign	0.058
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.020	B;B;B;B
Vest4		0.11
MutPred		0.32		Gain of glycosylation at Y9 (P = 0.0017);Gain of glycosylation at Y9 (P = 0.0017);Gain of glycosylation at Y9 (P = 0.0017);Gain of glycosylation at Y9 (P = 0.0017);
MVP		0.043
MPC		1.2
ClinPred		0.36	T
GERP RS		4.6
Varity_R		0.18
gMVP		0.35

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: rs532455340; hg19: chr3-150804729;