NM_030969.5:c.58G>A

Variant names:

• chr6-10749656-G-A
• rs1561913133
• NM_030969.5:c.58G>A

Variant summary

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

The NM_030969.5(TMEM14B):​c.58G>A​(p.Ala20Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM14B NM_030969.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

Genes affected

TMEM14B (HGNC:21384): (transmembrane protein 14B) Enables identical protein binding activity. Involved in cerebral cortex development; neural precursor cell proliferation; and regulation of G1/S transition of mitotic cell cycle. Predicted to be integral component of membrane. Predicted to be active in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272162 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM14B	NM_030969.5	c.58G>A	p.Ala20Thr	missense_variant	Exon 3 of 6	ENST00000379542.10	NP_112231.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM14B	ENST00000379542.10	c.58G>A	p.Ala20Thr	missense_variant	Exon 3 of 6	1	NM_030969.5	ENSP00000368858.5
ENSG00000272162	ENST00000480294.1	n.58G>A		non_coding_transcript_exon_variant	Exon 3 of 19	2		ENSP00000417929.1

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

May 03, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.58G>A (p.A20T) alteration is located in exon 3 (coding exon 2) of the TMEM14B gene. This alteration results from a G to A substitution at nucleotide position 58, causing the alanine (A) at amino acid position 20 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.;T;.;.;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T;T;T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T
MetaSVM	Benign	-0.67	T
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.8	D;D;D;D;N;N
REVEL	Benign	0.20
Sift	Benign	0.058	T;D;D;D;D;T
Sift4G	Benign	0.074	T;D;D;T;D;T
Polyphen		0.29	B;.;.;.;.;.
Vest4		0.46
MutPred		0.69		Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);
MVP		0.48
MPC		0.18
ClinPred		0.97	D
GERP RS		3.8
Varity_R		0.19
gMVP		0.045

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

LitVar

Other links and lift over

dbSNP: rs1561913133; hg19: chr6-10749889; COSMIC: COSV101077488; COSMIC: COSV101077488;