Variant chr7-66951043-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017994.5(TMEM248):c.688G>C(p.Ala230Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,460,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TMEM248
NM_017994.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51

Variant links:

Genes affected

TMEM248 (HGNC:25476): (transmembrane protein 248) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM248 links:

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ACMG classification

Classification made for transcript

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=0.30542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMEM248	NM_017994.5 linkuse as main transcript	c.688G>C	p.Ala230Pro	missense_variant	5/7	ENST00000341567.8
TMEM248	XM_024446819.2 linkuse as main transcript	c.712G>C	p.Ala238Pro	missense_variant	5/7
TMEM248	XM_024446820.2 linkuse as main transcript	c.688G>C	p.Ala230Pro	missense_variant	5/7
TMEM248	XM_024446821.2 linkuse as main transcript	c.688G>C	p.Ala230Pro	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM248	ENST00000341567.8 linkuse as main transcript	c.688G>C	p.Ala230Pro	missense_variant	5/7	1	NM_017994.5	P1	Q9NWD8-1
TMEM248	ENST00000433271.6 linkuse as main transcript	c.597-2183G>C		intron_variant, NMD_transcript_variant		1			Q9NWD8-2
TMEM248	ENST00000484751.1 linkuse as main transcript	n.447G>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250228

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135300

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1460838

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726726

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.688G>C (p.A230P) alteration is located in exon 5 (coding exon 4) of the TMEM248 gene. This alteration results from a G to C substitution at nucleotide position 688, causing the alanine (A) at amino acid position 230 to be replaced by a proline (P). 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

0.24

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

Eigen

Benign

0.021

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0028

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.31

REVEL

Benign

0.14

Sift

Benign

0.21

Sift4G

Benign

0.16

Polyphen

0.0050

Vest4

0.68

MVP

0.048

MPC

0.42

ClinPred

0.16

GERP RS

5.9

Varity_R

0.32

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over