chr1-32014308-C-T

Variant names:

• chr1-32014308-C-T
• NM_006559.3:c.313C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.18
• 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 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

Sel.	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

Sel.	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.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1406708 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 696696

African (AFR) AF: 0.00 AC: 0 AN: 31164

American (AMR) AF: 0.00 AC: 0 AN: 38270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25020

East Asian (EAS) AF: 0.00 AC: 0 AN: 35192

South Asian (SAS) AF: 0.00 AC: 0 AN: 79272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084470

Other (OTH) AF: 0.00 AC: 0 AN: 58050

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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.2
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.19
Sift	Benign	0.17	T
Sift4G	Benign	0.12	T
Polyphen		0.99	D
Vest4		0.39
MutPred		0.22		Gain of phosphorylation at P105 (P = 0.0371)
MVP		0.43
MPC		1.1
ClinPred		0.96	D
GERP RS		4.1
PromoterAI		-0.073	Neutral
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

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: chr1-32479909;