NM_006559.3:c.242C>G

Variant names:

• chr1-32014237-C-G
• NM_006559.3:c.242C>G

Variant summary

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

The NM_006559.3(KHDRBS1):​c.242C>G​(p.Pro81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,375,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P81L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: KHDRBS1 NM_006559.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=0.1412715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KHDRBS1	NM_006559.3	c.242C>G	p.Pro81Arg	missense_variant	Exon 1 of 9	ENST00000327300.12	NP_006550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KHDRBS1	ENST00000327300.12	c.242C>G	p.Pro81Arg	missense_variant	Exon 1 of 9	1	NM_006559.3	ENSP00000313829.7
KHDRBS1	ENST00000492989.1	c.242C>G	p.Pro81Arg	missense_variant	Exon 1 of 8	1		ENSP00000417731.1
KHDRBS1	ENST00000307714.12	n.312C>G		non_coding_transcript_exon_variant	Exon 1 of 9	1
KHDRBS1	ENST00000484270.2	n.56C>G		non_coding_transcript_exon_variant	Exon 1 of 11	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1375534 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 678540

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: 0.00

Gnomad4 OTH exome AF: 0.0000176

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.75	T;T
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.65	N;N
REVEL	Benign	0.069
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.0030	B;B
Vest4		0.18
MutPred		0.25		Gain of methylation at P81 (P = 0.0071);Gain of methylation at P81 (P = 0.0071);
MVP		0.46
MPC		1.1
ClinPred		0.37	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.14
gMVP		0.26

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: chr1-32479838;