7-66941941-A-G

Position:

• chr7-66941941-A-G

Variant summary

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

The NM_017994.5(TMEM248):​c.76A>G​(p.Ser26Gly) variant causes a missense change involving the alteration of a conserved nucleotide. 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: TMEM248 NM_017994.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.54

Genes affected

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

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/exons	MANE	UniProt
TMEM248	NM_017994.5	c.76A>G	p.Ser26Gly	missense_variant	2/7	ENST00000341567.8
TMEM248	XM_024446819.2	c.100A>G	p.Ser34Gly	missense_variant	2/7
TMEM248	XM_024446820.2	c.76A>G	p.Ser26Gly	missense_variant	2/7
TMEM248	XM_024446821.2	c.76A>G	p.Ser26Gly	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM248	ENST00000341567.8	c.76A>G	p.Ser26Gly	missense_variant	2/7	1	NM_017994.5	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2023

The c.76A>G (p.S26G) alteration is located in exon 2 (coding exon 1) of the TMEM248 gene. This alteration results from a A to G substitution at nucleotide position 76, causing the serine (S) at amino acid position 26 to be replaced by a glycine (G). 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	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T;T;T;.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.48	T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.2	M;.;.;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.0	N;.;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.096	T;.;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.89	P;.;.;.;.
Vest4		0.86
MutPred		0.34		Loss of stability (P = 0.201);Loss of stability (P = 0.201);Loss of stability (P = 0.201);Loss of stability (P = 0.201);Loss of stability (P = 0.201);
MVP		0.076
MPC		0.70
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.24
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-66406928;