chr1-32037040-C-A

Variant names:

• chr1-32037040-C-A
• NM_006559.3:c.902C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006559.3(KHDRBS1):​c.902C>A​(p.Pro301His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KHDRBS1 NM_006559.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61

Genes affected

KHDRBS1 (HGNC:18116): (KH RNA binding domain containing, signal transduction associated 1) This gene encodes a member of the K homology domain-containing, RNA-binding, signal transduction-associated protein family. The encoded protein appears to have many functions and may be involved in a variety of cellular processes, including alternative splicing, cell cycle regulation, RNA 3'-end formation, tumorigenesis, and regulation of human immunodeficiency virus gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1430259).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KHDRBS1	NM_006559.3	c.902C>A	p.Pro301His	missense_variant	Exon 5 of 9	ENST00000327300.12	NP_006550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KHDRBS1	ENST00000327300.12	c.902C>A	p.Pro301His	missense_variant	Exon 5 of 9	1	NM_006559.3	ENSP00000313829.7
KHDRBS1	ENST00000492989.1	c.785C>A	p.Pro262His	missense_variant	Exon 4 of 8	1		ENSP00000417731.1
KHDRBS1	ENST00000307714.12	n.972C>A		non_coding_transcript_exon_variant	Exon 5 of 9	1
KHDRBS1	ENST00000484270.2	n.716C>A		non_coding_transcript_exon_variant	Exon 5 of 11	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.902C>A (p.P301H) alteration is located in exon 5 (coding exon 5) of the KHDRBS1 gene. This alteration results from a C to A substitution at nucleotide position 902, causing the proline (P) at amino acid position 301 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.52	D;.
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.18
Sift	Benign	0.13	T;T
Sift4G	Uncertain	0.045	D;D
Polyphen		0.0030	B;B
Vest4		0.23
MutPred		0.16		Gain of MoRF binding (P = 0.0633);.;
MVP		0.36
MPC		1.5
ClinPred		0.74	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.12
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-32502641;