1-32014108-C-T

Variant names:

• chr1-32014108-C-T
• NM_006559.3:c.113C>T

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.113C>T​(p.Pro38Leu) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KHDRBS1 NM_006559.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73
• 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=0.19695291).

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.113C>T	p.Pro38Leu	missense	Exon 1 of 9	NP_006550.1	Q07666-1
	KHDRBS1	NM_001271878.2		c.113C>T	p.Pro38Leu	missense	Exon 1 of 8	NP_001258807.1	Q07666-3
	KHDRBS1	NR_073498.2		n.241C>T		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHDRBS1	ENST00000327300.12	TSL:1 MANE Select	c.113C>T	p.Pro38Leu	missense	Exon 1 of 9	ENSP00000313829.7	Q07666-1
	KHDRBS1	ENST00000492989.1	TSL:1	c.113C>T	p.Pro38Leu	missense	Exon 1 of 8	ENSP00000417731.1	Q07666-3
	KHDRBS1	ENST00000307714.12	TSL:1	n.183C>T		non_coding_transcript_exon	Exon 1 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1279304 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 629536

African (AFR) AF: 0.00 AC: 0 AN: 25872

American (AMR) AF: 0.00 AC: 0 AN: 20138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21934

East Asian (EAS) AF: 0.00 AC: 0 AN: 27720

South Asian (SAS) AF: 0.00 AC: 0 AN: 66404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1026044

Other (OTH) AF: 0.00 AC: 0 AN: 52310

GnomAD4 genome Cov.: 32

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	0.088
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.7
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.037
Sift	Uncertain	0.014	D
Sift4G	Benign	0.68	T
Polyphen		0.47	P
Vest4		0.22
MutPred		0.18		Loss of glycosylation at P38 (P = 0.0351)
MVP		0.46
MPC		1.1
ClinPred		0.54	D
GERP RS		4.0
PromoterAI		-0.067	Neutral
Varity_R		0.14
gMVP		0.38
Mutation Taster		=76/24	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: chr1-32479709;