rs4718428

Positions:

• chr7-66956459-T-A
• chr7-66956459-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017994.5(TMEM248):​c.*937T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000553 in 144,546 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000055 (0 hom., cov: 32)
• Consequence: TMEM248 NM_017994.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM248	NM_017994.5	c.*937T>A		3_prime_UTR_variant	7/7	ENST00000341567.8	NP_060464.1
TMEM248	XM_024446819.2	c.*937T>A		3_prime_UTR_variant	7/7		XP_024302587.1
TMEM248	XM_024446820.2	c.*937T>A		3_prime_UTR_variant	7/7		XP_024302588.1
TMEM248	XM_024446821.2	c.*937T>A		3_prime_UTR_variant	7/7		XP_024302589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM248	ENST00000341567.8	c.*937T>A		3_prime_UTR_variant	7/7	1	NM_017994.5	ENSP00000340668.4

Frequencies

GnomAD3 genomes AF: 0.0000485 AC: 7 AN: 144458 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000876

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000493

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000553 AC: 8 AN: 144546 Hom.: 0 Cov.: 32 AF XY: 0.0000424 AC XY: 3 AN XY: 70794

Gnomad4 AFR AF: 0.000117

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000488

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.17

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

LitVar

Other links and lift over

dbSNP: rs4718428; hg19: chr7-66421446;