rs5934953

Variant names:

• chrX-11030572-T-C
• rs5934953
• ENST00000433747.7:n.593+25364A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000433747.7(HCCS-DT):​n.593+25364A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 110,418 control chromosomes in the GnomAD database, including 27 homozygotes. There are 599 hemizygotes in GnomAD. 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 0.020 (27 hom., 599 hem., cov: 22)
• Consequence: HCCS-DT ENST00000433747.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 7 publications found

Genes affected

HCCS-DT (HGNC:55698): (HCCS divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0204 (2254/110418) while in subpopulation NFE AF = 0.0314 (1662/52911). AF 95% confidence interval is 0.0302. There are 27 homozygotes in GnomAd4. There are 599 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCCS-DT	NR_186561.1	n.500+8031A>G		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCCS-DT	ENST00000433747.7	n.593+25364A>G		intron_variant	Intron 3 of 3	1
HCCS-DT	ENST00000608176.5	n.317+76329A>G		intron_variant	Intron 2 of 3	5
HCCS-DT	ENST00000608576.6	n.615+25364A>G		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 2255 AN: 110370 Hom.: 27 Cov.: 22

Gnomad AFR AF: 0.00406

Gnomad AMI AF: 0.00732

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.000283

Gnomad SAS AF: 0.00773

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0294

Gnomad NFE AF: 0.0314

Gnomad OTH AF: 0.0204

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

GnomAD4 genome AF: 0.0204 AC: 2254 AN: 110418 Hom.: 27 Cov.: 22 AF XY: 0.0183 AC XY: 599 AN XY: 32672

African (AFR) AF: 0.00405 AC: 123 AN: 30353

American (AMR) AF: 0.0196 AC: 201 AN: 10281

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 118 AN: 2641

East Asian (EAS) AF: 0.000284 AC: 1 AN: 3527

South Asian (SAS) AF: 0.00815 AC: 21 AN: 2578

European-Finnish (FIN) AF: 0.0153 AC: 88 AN: 5740

Middle Eastern (MID) AF: 0.0231 AC: 5 AN: 216

European-Non Finnish (NFE) AF: 0.0314 AC: 1662 AN: 52911

Other (OTH) AF: 0.0202 AC: 30 AN: 1488

Alfa AF: 0.0273 Hom.: 1840

Bravo AF: 0.0199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.093
DANN	Benign	0.47
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs5934953; hg19: chrX-11048692;