dbSNP rs463260: WDR46:c.-37G>T (chr6-33289207-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005452.6(WDR46):c.-37G>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WDR46
NM_005452.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

0 publications found

Variant links:

Genes affected

WDR46 (HGNC:13923): (WD repeat domain 46) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleoplasm. Predicted to be part of small-subunit processome. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

WDR46 links:

PFDN6 (HGNC:4926): (prefoldin subunit 6) PFDN6 is a subunit of the heteromeric prefoldin complex that chaperones nascent actin (see MIM 102560) and alpha- and beta-tubulin (see MIM 602529 and MIM 191130, respectively) chains pending their transfer to the cytosolic chaperonin containing TCP1 (MIM 186980) (CCT) complex (Hansen et al., 1999 [PubMed 10209023]).[supplied by OMIM, Jul 2010]

PFDN6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005452.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDR46	NM_005452.6	MANE Select	c.-37G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_005443.3
WDR46	NM_005452.6	MANE Select	c.-37G>T	5_prime_UTR	Exon 1 of 15	NP_005443.3
WDR46	NM_001164267.2		c.-37G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_001157739.1	A0A1U9X8W1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDR46	ENST00000374617.9	TSL:1 MANE Select	c.-37G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000363746.4	O15213
WDR46	ENST00000374617.9	TSL:1 MANE Select	c.-37G>T	5_prime_UTR	Exon 1 of 15	ENSP00000363746.4	O15213
PFDN6	ENST00000883725.1		c.-161C>A	5_prime_UTR	Exon 1 of 5	ENSP00000553784.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1441064

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715772

African (AFR)

AF:

0.00

AC:

AN:

32574

American (AMR)

AF:

0.00

AC:

AN:

40758

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25130

East Asian (EAS)

AF:

0.00

AC:

AN:

39444

South Asian (SAS)

AF:

0.00

AC:

AN:

84502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5526

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102466

Other (OTH)

AF:

0.00

AC:

AN:

59478

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

4.2

(source)

DANN

Benign

0.78

PhyloP100

-1.2

PromoterAI

0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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