16-8589749-G-A

Position:

• chr16-8589749-G-A

Variant summary

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

The NM_001146336.2(TMEM114):​c.90C>T​(p.Asp30=) 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: TMEM114 NM_001146336.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.82

Genes affected

TMEM114 (HGNC:33227): (transmembrane protein 114) This gene encodes a glycosylated transmembrane protein that plays a role in lens and eye development. Mutations in this gene, including a t(16;22)(p13.3;q11.2) translocation, are associated with congenital and juvenile cataract disorders. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (Cadd=11.76).
• BP6: Variant 16-8589749-G-A is Benign according to our data. Variant chr16-8589749-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3054083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.82 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM114	NM_001146336.2	c.90C>T	p.Asp30=	synonymous_variant	1/4	ENST00000620492.5	NP_001139808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM114	ENST00000620492.5	c.90C>T	p.Asp30=	synonymous_variant	1/4	2	NM_001146336.2	ENSP00000484263	P1
TMEM114	ENST00000624696.1	c.90C>T	p.Asp30=	synonymous_variant	1/3	2		ENSP00000485294
TMEM114	ENST00000568335.3	c.-24+271C>T		intron_variant		3		ENSP00000454261
TMEM114	ENST00000623677.1	n.1C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TMEM114-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 03, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	12

Splicing

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: -;