1-28334579-C-T

Variant names:

• chr1-28334579-C-T
• NM_017638.3:c.236C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017638.3(MED18):​c.236C>T​(p.Ala79Val) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MED18 NM_017638.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60

Genes affected

MED18 (HGNC:25944): (mediator complex subunit 18) MED18 is a component of the Mediator complex, which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II (Sato et al., 2003 [PubMed 12584197]).[supplied by OMIM, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11459488).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED18	NM_017638.3	c.236C>T	p.Ala79Val	missense_variant	Exon 3 of 3	ENST00000373842.9	NP_060108.2
MED18	NM_001127350.2	c.236C>T	p.Ala79Val	missense_variant	Exon 3 of 3		NP_001120822.1
MED18	XM_005245914.5	c.236C>T	p.Ala79Val	missense_variant	Exon 3 of 3		XP_005245971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED18	ENST00000373842.9	c.236C>T	p.Ala79Val	missense_variant	Exon 3 of 3	2	NM_017638.3	ENSP00000362948.4
MED18	ENST00000398997.2	c.236C>T	p.Ala79Val	missense_variant	Exon 3 of 4	5		ENSP00000381963.2
MED18	ENST00000474683.1	n.395C>T		non_coding_transcript_exon_variant	Exon 3 of 3	3
MED18	ENST00000479574.5	n.425C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.236C>T (p.A79V) alteration is located in exon 3 (coding exon 2) of the MED18 gene. This alteration results from a C to T substitution at nucleotide position 236, causing the alanine (A) at amino acid position 79 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.086
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.55	N;N
REVEL	Benign	0.033
Sift	Benign	0.17	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.033	B;B
Vest4		0.14
MutPred		0.27		Loss of disorder (P = 0.0572);Loss of disorder (P = 0.0572);
MVP		0.21
MPC		0.53
ClinPred		0.48	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.050
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-28661090;