Genetic Variant NM_006559.3:c.313C>T (chr1-32014308-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_006559.3(KHDRBS1):c.313C>T(p.Pro105Ser) 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KHDRBS1
NM_006559.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.18

Publications

0 publications found

Variant links:

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]

KHDRBS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 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=0.36388582).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KHDRBS1	NM_006559.3	MANE Select	c.313C>T	p.Pro105Ser	missense	Exon 1 of 9	NP_006550.1	Q07666-1
KHDRBS1	NM_001271878.2		c.313C>T	p.Pro105Ser	missense	Exon 1 of 8	NP_001258807.1	Q07666-3
KHDRBS1	NR_073498.2		n.441C>T		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KHDRBS1	ENST00000327300.12	TSL:1 MANE Select	c.313C>T	p.Pro105Ser	missense	Exon 1 of 9	ENSP00000313829.7	Q07666-1
KHDRBS1	ENST00000492989.1	TSL:1	c.313C>T	p.Pro105Ser	missense	Exon 1 of 8	ENSP00000417731.1	Q07666-3
KHDRBS1	ENST00000307714.12	TSL:1	n.383C>T		non_coding_transcript_exon	Exon 1 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1406708

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696696

African (AFR)

AF:

0.00

AC:

AN:

31164

American (AMR)

AF:

0.00

AC:

AN:

38270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25020

East Asian (EAS)

AF:

0.00

AC:

AN:

35192

South Asian (SAS)

AF:

0.00

AC:

AN:

79272

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084470

Other (OTH)

AF:

0.00

AC:

AN:

58050

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.60

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.0

PhyloP100

5.2

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.19

Sift

Benign

0.17

Sift4G

Benign

0.12

Polyphen

0.99

Vest4

0.39

MutPred

0.22

Gain of phosphorylation at P105 (P = 0.0371)

MVP

0.43

MPC

1.1

ClinPred

0.96

GERP RS

4.1

PromoterAI

-0.073

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.44

gMVP

0.51

Mutation Taster

=30/70

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over