rs1450112631

Variant names:

• chr19-49831338-C-T
• rs1450112631
• NM_030973.4:c.1107C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-49831338-C-T
• chr19-49831338-C-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_030973.4(MED25):​c.1107C>T​(p.Gly369Gly) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MED25 NM_030973.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.535
• Publications: 0 publications found

Genes affected

MED25 (HGNC:28845): (mediator complex subunit 25) This gene encodes a component of the transcriptional coactivator complex termed the Mediator complex. This complex is required for transcription of most RNA polymerase II-dependent genes. The encoded protein plays a role in chromatin modification and in preinitiation complex assembly. Mutations in this gene are associated with Charcot-Marie-Tooth disease type 2B2. [provided by RefSeq, Apr 2010]

MED25 Gene-Disease associations (from GenCC):

• congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Charcot-Marie-Tooth disease type 2B2

  Inheritance: AR Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 19-49831338-C-T is Benign according to our data. Variant chr19-49831338-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 543188.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.535 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030973.4. 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
	MED25	NM_030973.4	MANE Select	c.1107C>T	p.Gly369Gly	synonymous	Exon 10 of 18	NP_112235.2	Q71SY5-1
	MED25	NM_001378355.1		c.1107C>T	p.Gly369Gly	synonymous	Exon 10 of 18	NP_001365284.1	M0QZQ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED25	ENST00000312865.10	TSL:1 MANE Select	c.1107C>T	p.Gly369Gly	synonymous	Exon 10 of 18	ENSP00000326767.5	Q71SY5-1
	MED25	ENST00000538643.5	TSL:1	c.468C>T	p.Gly156Gly	synonymous	Exon 5 of 13	ENSP00000437496.1	Q71SY5-6
	MED25	ENST00000595185.5	TSL:1	c.688+1390C>T		intron	N/A	ENSP00000470027.1	M0QYR4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 239346 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Charcot-Marie-Tooth disease type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.62
PhyloP100		0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1450112631; hg19: chr19-50334595;