chr8-108734826-T-C

Position:

• chr8-108734826-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000518838.1(TMEM74):​n.119+52650A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 152,246 control chromosomes in the GnomAD database, including 323 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 0.042 (323 hom., cov: 32)
• Consequence: TMEM74 ENST00000518838.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

Genes affected

TMEM74 (HGNC:26409): (transmembrane protein 74) Involved in macroautophagy. Predicted to be located in autophagosome membrane; cytoplasmic vesicle; and lysosomal membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM74	NR_136411.2	n.119+52650A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM74	ENST00000518838.1	n.119+52650A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0416 AC: 6332 AN: 152128 Hom.: 320 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00938

Gnomad OTH AF: 0.0449

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0418 AC: 6363 AN: 152246 Hom.: 323 Cov.: 32 AF XY: 0.0416 AC XY: 3096 AN XY: 74440

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0275

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00938

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0284 Hom.: 23

Bravo AF: 0.0459

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9297417; hg19: chr8-109747055;