chr19-6415432-T-C

Position:

• chr19-6415432-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001366299.1(KHSRP):​c.1914A>G​(p.Ala638Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,576,760 control chromosomes in the GnomAD database, including 762,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (72885 hom., cov: 35)
  • Exomes 𝑓: 0.98 (689442 hom.)
• Consequence: KHSRP NM_001366299.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -8.65

Genes affected

KHSRP (HGNC:6316): (KH-type splicing regulatory protein) The KHSRP gene encodes a multifunctional RNA-binding protein implicated in a variety of cellular processes, including transcription, alternative pre-mRNA splicing, and mRNA localization (Min et al., 1997 [PubMed 9136930]; Gherzi et al., 2004 [PubMed 15175153]).[supplied by OMIM, Apr 2010]

KHSRP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-6415432-T-C is Benign according to our data. Variant chr19-6415432-T-C is described in ClinVar as [Benign]. Clinvar id is 1246901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-8.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHSRP	NM_001366299.1	c.1914A>G	p.Ala638Ala	synonymous_variant	18/19	ENST00000600480.2	NP_001353228.1
KHSRP	NM_003685.3	c.1914A>G	p.Ala638Ala	synonymous_variant	18/20		NP_003676.2
KHSRP	NM_001366300.1	c.1839A>G	p.Ala613Ala	synonymous_variant	18/20		NP_001353229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHSRP	ENST00000600480.2	c.1914A>G	p.Ala638Ala	synonymous_variant	18/19	2	NM_001366299.1	ENSP00000471146.2

Frequencies

GnomAD3 genomes AF: 0.978 AC: 148901 AN: 152250 Hom.: 72834 Cov.: 35

Gnomad AFR AF: 0.957

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.984

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.992

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.979

GnomAD3 exomes AF: 0.984 AC: 185894 AN: 188956 Hom.: 91458 AF XY: 0.983 AC XY: 100329 AN XY: 102034

Gnomad AFR exome AF: 0.954

Gnomad AMR exome AF: 0.992

Gnomad ASJ exome AF: 0.989

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.972

Gnomad FIN exome AF: 0.992

Gnomad NFE exome AF: 0.983

Gnomad OTH exome AF: 0.989

GnomAD4 exome AF: 0.984 AC: 1401385 AN: 1424392 Hom.: 689442 Cov.: 80 AF XY: 0.984 AC XY: 693729 AN XY: 705170

Gnomad4 AFR exome AF: 0.956

Gnomad4 AMR exome AF: 0.992

Gnomad4 ASJ exome AF: 0.989

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.972

Gnomad4 FIN exome AF: 0.991

Gnomad4 NFE exome AF: 0.984

Gnomad4 OTH exome AF: 0.985

GnomAD4 genome AF: 0.978 AC: 149011 AN: 152368 Hom.: 72885 Cov.: 35 AF XY: 0.978 AC XY: 72875 AN XY: 74512

Gnomad4 AFR AF: 0.957

Gnomad4 AMR AF: 0.984

Gnomad4 ASJ AF: 0.988

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.992

Gnomad4 NFE AF: 0.985

Gnomad4 OTH AF: 0.977

Alfa AF: 0.982 Hom.: 33143

Bravo AF: 0.977

Asia WGS AF: 0.979 AC: 3406 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.62

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: rs1616305; hg19: chr19-6415443;