rs777298003

Variant names:

• chr19-39391415-C-G
• rs777298003
• ENST00000615911.4:c.56C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-39391415-C-G
• chr19-39391415-C-A
• chr19-39391415-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000615911.4(MED29):​c.56C>G​(p.Ala19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,611,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MED29 ENST00000615911.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.51
• Publications: 2 publications found

Genes affected

MED29 (HGNC:23074): (mediator complex subunit 29) MED29 is a subunit of the Mediator complex, a multiprotein coactivator of RNA transcription that interacts with DNA-bound transcriptional activators, RNA polymerase II (see MIM 180660), and general initiation factors (Sato et al., 2003 [PubMed 14576168]).[supplied by OMIM, Aug 2009]

ENSG00000307007 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04423526).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000615911.4. 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
	MED29	NM_017592.4	MANE Select	c.-8C>G		5_prime_UTR	Exon 1 of 4	NP_060062.2	Q9NX70-1
	MED29	NM_001317770.3		c.-8C>G		5_prime_UTR	Exon 1 of 4	NP_001304699.2	Q9NX70-2
	MED29	NR_133915.3		n.38C>G		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED29	ENST00000615911.4	TSL:1	c.56C>G	p.Ala19Gly	missense	Exon 1 of 4	ENSP00000481733.1	B4DUA7
	MED29	ENST00000315588.11	TSL:1 MANE Select	c.-8C>G		5_prime_UTR	Exon 1 of 4	ENSP00000314343.5	Q9NX70-1
	MED29	ENST00000596297.1	TSL:5	c.-8C>G		5_prime_UTR	Exon 1 of 4	ENSP00000473181.2	M0R3F3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152226 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250182 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459162 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725270

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109882

Other (OTH) AF: 0.00 AC: 0 AN: 60274

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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	0.088
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.6
DANN	Uncertain	0.98
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.054
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.039	B
Vest4		0.25
MutPred		0.099		Gain of methylation at R20 (P = 0.0602)
MVP		0.067
MPC		0.45
ClinPred		0.91	D
GERP RS		-6.3
PromoterAI		0.074	Neutral
gMVP		0.21
Mutation Taster		=99/1	polymorphism

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: rs777298003; hg19: chr19-39882055;