NM_006559.3:c.902C>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.4159 (below the threshold of 3.09). Trascript score misZ: 0.57108 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.1430259).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006559.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHDRBS1	NM_006559.3	MANE Select	c.902C>A	p.Pro301His	missense	Exon 5 of 9	NP_006550.1	Q07666-1
	KHDRBS1	NM_001271878.2		c.785C>A	p.Pro262His	missense	Exon 4 of 8	NP_001258807.1	Q07666-3
	KHDRBS1	NR_073498.2		n.1030C>A		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHDRBS1	ENST00000327300.12	TSL:1 MANE Select	c.902C>A	p.Pro301His	missense	Exon 5 of 9	ENSP00000313829.7	Q07666-1
	KHDRBS1	ENST00000492989.1	TSL:1	c.785C>A	p.Pro262His	missense	Exon 4 of 8	ENSP00000417731.1	Q07666-3
	KHDRBS1	ENST00000307714.12	TSL:1	n.972C>A		non_coding_transcript_exon	Exon 5 of 9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.18
Sift	Benign	0.13	T
Sift4G	Uncertain	0.045	D
Polyphen		0.0030	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
Mutation Taster		=68/32	polymorphism

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

hg19: chr1-32502641;