chr6-10751180-G-A

Variant names:

• chr6-10751180-G-A
• rs146152247
• NM_030969.5:c.148G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_030969.5(TMEM14B):​c.148G>A​(p.Gly50Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000627 in 1,613,960 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (1 hom.)
• Consequence: TMEM14B NM_030969.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.65
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030969.5. 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
	TMEM14B	NM_030969.5	MANE Select	c.148G>A	p.Gly50Ser	missense	Exon 4 of 6	NP_112231.3
	TMEM14B	NM_001286488.2		c.148G>A	p.Gly50Ser	missense	Exon 4 of 6	NP_001273417.1	C9JCY4
	TMEM14B	NM_001286484.2		c.115G>A	p.Gly39Ser	missense	Exon 3 of 5	NP_001273413.1	A0A087WU83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM14B	ENST00000379542.10	TSL:1 MANE Select	c.148G>A	p.Gly50Ser	missense	Exon 4 of 6	ENSP00000368858.5	Q9NUH8-1
	TMEM14B	ENST00000463448.5	TSL:1	n.100+1482G>A		intron	N/A	ENSP00000419208.1	F2Z2F8
	ENSG00000272162	ENST00000480294.1	TSL:2	n.100+1482G>A		intron	N/A	ENSP00000417929.1	F8WBI7

Frequencies

GnomAD3 genomes AF: 0.000428 AC: 65 AN: 152010 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000334 AC: 84 AN: 251466 AF XY: 0.000375

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000703

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000648 AC: 947 AN: 1461832 Hom.: 1 Cov.: 30 AF XY: 0.000638 AC XY: 464 AN XY: 727214

African (AFR) AF: 0.0000897 AC: 3 AN: 33462

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53410

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.000817 AC: 909 AN: 1111996

Other (OTH) AF: 0.000447 AC: 27 AN: 60388

GnomAD4 genome AF: 0.000427 AC: 65 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74378

African (AFR) AF: 0.0000724 AC: 3 AN: 41438

American (AMR) AF: 0.000131 AC: 2 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000514 Hom.: 0

Bravo AF: 0.000382

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000387 AC: 47

EpiCase AF: 0.000654

EpiControl AF: 0.000356

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.1	T
PhyloP100		7.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.24
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.016	D
Polyphen		0.94	P
Vest4		0.84
MVP		0.37
MPC		0.15
ClinPred		0.33	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.091
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs146152247; hg19: chr6-10751413; COSMIC: COSV99058835; COSMIC: COSV99058835;