19-39397750-G-C

Variant names:

• chr19-39397750-G-C
• rs1057745
• NM_017592.4:c.*51G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017592.4(MED29):​c.*51G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,583,642 control chromosomes in the GnomAD database, including 11,589 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1111 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10478 hom.)
• Consequence: MED29 NM_017592.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 19 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016457736).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED29	NM_017592.4	c.*51G>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000315588.11	NP_060062.2
MED29	NM_001317770.3	c.584G>C	p.Arg195Thr	missense_variant	Exon 4 of 4		NP_001304699.2
MED29	NR_133915.3	n.640G>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED29	ENST00000315588.11	c.*51G>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_017592.4	ENSP00000314343.5

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16797 AN: 152136 Hom.: 1106 Cov.: 33

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.0938

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.133 AC: 29748 AN: 223090 AF XY: 0.131

Gnomad AFR exome AF: 0.0957

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.0548

Gnomad EAS exome AF: 0.0902

Gnomad FIN exome AF: 0.0654

Gnomad NFE exome AF: 0.0972

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.114 AC: 162490 AN: 1431388 Hom.: 10478 Cov.: 32 AF XY: 0.115 AC XY: 81645 AN XY: 709912

African (AFR) AF: 0.0900 AC: 2990 AN: 33212

American (AMR) AF: 0.264 AC: 11341 AN: 43002

Ashkenazi Jewish (ASJ) AF: 0.0540 AC: 1376 AN: 25458

East Asian (EAS) AF: 0.0786 AC: 3082 AN: 39216

South Asian (SAS) AF: 0.196 AC: 16612 AN: 84972

European-Finnish (FIN) AF: 0.0681 AC: 2683 AN: 39404

Middle Eastern (MID) AF: 0.103 AC: 590 AN: 5702

European-Non Finnish (NFE) AF: 0.106 AC: 116775 AN: 1100844

Other (OTH) AF: 0.118 AC: 7041 AN: 59578

GnomAD4 genome AF: 0.110 AC: 16812 AN: 152254 Hom.: 1111 Cov.: 33 AF XY: 0.112 AC XY: 8364 AN XY: 74450

African (AFR) AF: 0.0928 AC: 3857 AN: 41548

American (AMR) AF: 0.209 AC: 3202 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0571 AC: 198 AN: 3470

East Asian (EAS) AF: 0.0927 AC: 480 AN: 5180

South Asian (SAS) AF: 0.199 AC: 961 AN: 4824

European-Finnish (FIN) AF: 0.0694 AC: 738 AN: 10628

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6948 AN: 67998

Other (OTH) AF: 0.117 AC: 246 AN: 2108

Alfa AF: 0.0585 Hom.: 83

Bravo AF: 0.121

TwinsUK AF: 0.108 AC: 402

ALSPAC AF: 0.115 AC: 445

ESP6500AA AF: 0.0893 AC: 393

ESP6500EA AF: 0.102 AC: 879

ExAC AF: 0.119 AC: 14432

Asia WGS AF: 0.182 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.9
DANN	Benign	0.75
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0016	T
PhyloP100		1.0
PrimateAI	Benign	0.30	T
Vest4		0.18
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=93/7	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: rs1057745; hg19: chr19-39888390; COSMIC: COSV107323581; COSMIC: COSV107323581;