chr6-10749669-C-A

Variant names:

• chr6-10749669-C-A
• rs776913086
• NM_030969.5:c.71C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030969.5(TMEM14B):​c.71C>A​(p.Ser24Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM14B NM_030969.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41904435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM14B	NM_030969.5	c.71C>A	p.Ser24Tyr	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.71C>A	p.Ser24Tyr	missense_variant	Exon 3 of 6	1	NM_030969.5	ENSP00000368858.5
ENSG00000272162	ENST00000480294.1	n.71C>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

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;.;T;.;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.42	T;T;T;T;T;T
MetaSVM	Benign	-0.72	T
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.6	D;D;D;D;N;D
REVEL	Benign	0.21
Sift	Benign	0.051	T;D;T;D;D;T
Sift4G	Benign	0.57	T;D;T;D;D;D
Polyphen		0.99	D;.;.;.;.;.
Vest4		0.53
MutPred		0.44		Loss of glycosylation at S24 (P = 0.003);Loss of glycosylation at S24 (P = 0.003);Loss of glycosylation at S24 (P = 0.003);Loss of glycosylation at S24 (P = 0.003);Loss of glycosylation at S24 (P = 0.003);Loss of glycosylation at S24 (P = 0.003);
MVP		0.41
MPC		0.36
ClinPred		0.98	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.37
gMVP		0.092

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs776913086; hg19: chr6-10749902;