rs1060504702

Variant names:

• chr12-116277075-G-A
• rs1060504702
• NM_015335.5:c.57C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-116277075-G-A
• chr12-116277075-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_015335.5(MED13L):​c.57C>T​(p.Ser19Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,439,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S19S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MED13L NM_015335.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44
• Publications: 0 publications found

Genes affected

MED13L (HGNC:22962): (mediator complex subunit 13L) The protein encoded by this gene is a subunit of the Mediator complex, a large complex of proteins that functions as a transcriptional coactivator for most RNA polymerase II-transcribed genes. The encoded protein is involved in early development of the heart and brain. Defects in this gene are a cause of transposition of the great arteries, dextro-looped (DTGA).[provided by RefSeq, Jul 2010]

MED13L Gene-Disease associations (from GenCC):

• cardiac anomalies - developmental delay - facial dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina, Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000299468 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=3.44 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED13L	NM_015335.5	c.57C>T	p.Ser19Ser	synonymous_variant	Exon 1 of 31	ENST00000281928.9	NP_056150.1
MED13L	XM_017019090.2	c.57C>T	p.Ser19Ser	synonymous_variant	Exon 1 of 31		XP_016874579.1
MED13L	XM_047428608.1	c.-108C>T		5_prime_UTR_variant	Exon 1 of 30		XP_047284564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED13L	ENST00000281928.9	c.57C>T	p.Ser19Ser	synonymous_variant	Exon 1 of 31	1	NM_015335.5	ENSP00000281928.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1439478 Hom.: 0 Cov.: 34 AF XY: 0.00000140 AC XY: 1 AN XY: 713814

African (AFR) AF: 0.00 AC: 0 AN: 33192

American (AMR) AF: 0.00 AC: 0 AN: 42372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25616

East Asian (EAS) AF: 0.00 AC: 0 AN: 38766

South Asian (SAS) AF: 0.00 AC: 0 AN: 82966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5148

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1102038

Other (OTH) AF: 0.00 AC: 0 AN: 59494

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Uncertain	0.98
PhyloP100		3.4
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7

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: rs1060504702; hg19: chr12-116714880;