rs3742575

Variant names:

• chr14-56650981-G-A
• rs3742575
• ENST00000554597.5:n.370-1853C>T

Variant summary

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

The ENST00000554597.5(ENSG00000259133):​n.370-1853C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,060 control chromosomes in the GnomAD database, including 6,888 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 0.27 (6888 hom., cov: 32)
• Consequence: ENSG00000259133 ENST00000554597.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 0 publications found

Genes affected

ENSG00000259133 (HGNC:):

TMEM260 (HGNC:20185): (transmembrane protein 260) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM260 Gene-Disease associations (from GenCC):

• structural heart defects and renal anomalies syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM260	XR_007064017.1	n.1987-9558G>A		intron_variant	Intron 15 of 16
TMEM260	XM_011536851.3	c.*868G>A		downstream_gene_variant			XP_011535153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000259133	ENST00000554597.5	n.370-1853C>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40456 AN: 151942 Hom.: 6887 Cov.: 32

Gnomad AFR AF: 0.0709

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.266 AC: 40445 AN: 152060 Hom.: 6888 Cov.: 32 AF XY: 0.265 AC XY: 19671 AN XY: 74334

African (AFR) AF: 0.0707 AC: 2934 AN: 41504

American (AMR) AF: 0.217 AC: 3312 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3464

East Asian (EAS) AF: 0.130 AC: 673 AN: 5166

South Asian (SAS) AF: 0.297 AC: 1431 AN: 4818

European-Finnish (FIN) AF: 0.350 AC: 3690 AN: 10554

Middle Eastern (MID) AF: 0.228 AC: 66 AN: 290

European-Non Finnish (NFE) AF: 0.390 AC: 26544 AN: 67982

Other (OTH) AF: 0.254 AC: 538 AN: 2114

Alfa AF: 0.315 Hom.: 1048

Bravo AF: 0.247

Asia WGS AF: 0.176 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.26
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs3742575; hg19: chr14-57117699;