7-66956459-T-G

Variant names:

• chr7-66956459-T-G
• rs4718428
• NM_017994.5:c.*937T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017994.5(TMEM248):​c.*937T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 144,468 control chromosomes in the GnomAD database, including 11,114 homozygotes. 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: 𝑓 0.39 (11114 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: TMEM248 NM_017994.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 22 publications found

Genes affected

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

ENSG00000299767 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM248	NM_017994.5	c.*937T>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000341567.8	NP_060464.1
TMEM248	XM_024446819.2	c.*937T>G		3_prime_UTR_variant	Exon 7 of 7		XP_024302587.1
TMEM248	XM_024446820.2	c.*937T>G		3_prime_UTR_variant	Exon 7 of 7		XP_024302588.1
TMEM248	XM_024446821.2	c.*937T>G		3_prime_UTR_variant	Exon 7 of 7		XP_024302589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM248	ENST00000341567.8	c.*937T>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_017994.5	ENSP00000340668.4
ENSG00000299767	ENST00000766237.1	n.463+4276A>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 56566 AN: 144378 Hom.: 11098 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.392 AC: 56617 AN: 144466 Hom.: 11114 Cov.: 32 AF XY: 0.399 AC XY: 28236 AN XY: 70748

African (AFR) AF: 0.384 AC: 13171 AN: 34294

American (AMR) AF: 0.434 AC: 6510 AN: 15010

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1673 AN: 3456

East Asian (EAS) AF: 0.712 AC: 3676 AN: 5162

South Asian (SAS) AF: 0.459 AC: 2211 AN: 4820

European-Finnish (FIN) AF: 0.406 AC: 4295 AN: 10566

Middle Eastern (MID) AF: 0.563 AC: 162 AN: 288

European-Non Finnish (NFE) AF: 0.348 AC: 23668 AN: 67916

Other (OTH) AF: 0.429 AC: 878 AN: 2046

Alfa AF: 0.360 Hom.: 27999

Bravo AF: 0.374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.43
PhyloP100		-0.021
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4718428; hg19: chr7-66421446;