dbSNP rs1012535544: KHDRBS1:p.Ala55Gly (chr1-32014159-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006559.3(KHDRBS1):c.164C>G(p.Ala55Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000174 in 1,151,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A55V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

KHDRBS1
NM_006559.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.409

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 made for transcript

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=0.22639224).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KHDRBS1	NM_006559.3 link	c.164C>G	p.Ala55Gly	missense_variant	Exon 1 of 9	ENST00000327300.12	NP_006550.1	Q07666-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KHDRBS1	ENST00000327300.12 link	c.164C>G	p.Ala55Gly	missense_variant	Exon 1 of 9	1	NM_006559.3	ENSP00000313829.7	Q07666-1
KHDRBS1	ENST00000492989.1 link	c.164C>G	p.Ala55Gly	missense_variant	Exon 1 of 8	1		ENSP00000417731.1	Q07666-3
KHDRBS1	ENST00000307714.12 link	n.234C>G		non_coding_transcript_exon_variant	Exon 1 of 9	1
KHDRBS1	ENST00000484270.2 link	n.-23C>G		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000174

AC:

AN:

1151252

Hom.:

Cov.:

AF XY:

0.00000361

AC XY:

AN XY:

553356

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000209

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-0.092

Eigen_PC

Benign

-0.062

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.74

T;T

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.34

N;N

REVEL

Benign

0.074

Sift

Benign

0.41

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.95

P;D

Vest4

0.14

MutPred

0.17

Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);

MVP

0.56

MPC

1.0

ClinPred

0.20

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.11

gMVP

0.16

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over