rs6997956

Positions:

• chr8-135472147-T-A
• chr8-135472147-T-G

Variant summary

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

The NM_006558.3(KHDRBS3):​c.88+14193T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,090 control chromosomes in the GnomAD database, including 11,643 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 0.37 (11643 hom., cov: 32)
• Consequence: KHDRBS3 NM_006558.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914

Genes affected

KHDRBS3 (HGNC:18117): (KH RNA binding domain containing, signal transduction associated 3) Enables RNA binding activity; identical protein binding activity; and protein domain specific binding activity. Predicted to be involved in regulation of alternative mRNA splicing, via spliceosome and spermatogenesis. Located in nucleoplasm. Part of protein-containing complex. [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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KHDRBS3	NM_006558.3	c.88+14193T>A		intron_variant		ENST00000355849.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KHDRBS3	ENST00000355849.10	c.88+14193T>A		intron_variant		1	NM_006558.3	P1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56317 AN: 151970 Hom.: 11640 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.370 AC: 56332 AN: 152090 Hom.: 11643 Cov.: 32 AF XY: 0.376 AC XY: 27986 AN XY: 74336

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.387

Alfa AF: 0.403 Hom.: 1646

Bravo AF: 0.359

Asia WGS AF: 0.472 AC: 1640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.2
DANN	Benign	0.86

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: rs6997956; hg19: chr8-136484390;