19-6422877-T-G

Variant names:

• chr19-6422877-T-G
• rs2075755
• NM_001366299.1:c.250-441A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001366299.1(KHSRP):​c.250-441A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: KHSRP NM_001366299.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366299.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHSRP	NM_001366299.1	MANE Select	c.250-441A>C		intron	N/A	NP_001353228.1
	KHSRP	NM_003685.3		c.250-441A>C		intron	N/A	NP_003676.2
	KHSRP	NM_001366300.1		c.250-441A>C		intron	N/A	NP_001353229.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHSRP	ENST00000600480.2	TSL:2 MANE Select	c.250-441A>C		intron	N/A	ENSP00000471146.2
	KHSRP	ENST00000398148.7	TSL:1	c.250-441A>C		intron	N/A	ENSP00000381216.2
	KHSRP	ENST00000599395.5	TSL:5	c.76-441A>C		intron	N/A	ENSP00000471262.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.2
DANN	Benign	0.72
PhyloP100		-0.61

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

Other links and lift over

dbSNP: rs2075755; hg19: chr19-6422888;