7-72777481-C-T

Variant names:

• chr7-72777481-C-T
• NM_001145440.3:c.899G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001145440.3(TYW1B):​c.899G>A​(p.Arg300Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TYW1B NM_001145440.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.752

Genes affected

TYW1B (HGNC:33908): (tRNA-yW synthesizing protein 1 homolog B) Wybutosine is a hypermodified guanosine found in phenylalanine tRNA. Wybutosine functions to stabilize codon-anticodon interactions during ribosome decoding and therefore supports the maintenance of the reading frame. In yeast, the homolog of this gene is essential for the synthesis of wybutosine. The human genome contains two closely related genes that putatively function in wybutosine synthesis. The open reading frame of this locus is disrupted in some individuals. Thus, this locus appears to be an evolving pseudogene, but may still be functional in some members of the population. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11208239).
• BP6: Variant 7-72777481-C-T is Benign according to our data. Variant chr7-72777481-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2340518.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYW1B	NM_001145440.3	c.899G>A	p.Arg300Lys	missense_variant	Exon 7 of 14	ENST00000620995.5	NP_001138912.2
TYW1B	NM_001412179.1	c.899G>A	p.Arg300Lys	missense_variant	Exon 7 of 12		NP_001399108.1
TYW1B	NM_001412180.1	c.899G>A	p.Arg300Lys	missense_variant	Exon 7 of 11		NP_001399109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYW1B	ENST00000620995.5	c.899G>A	p.Arg300Lys	missense_variant	Exon 7 of 14	1	NM_001145440.3	ENSP00000482502.1
TYW1B	ENST00000612372.4	c.413G>A	p.Arg138Lys	missense_variant	Exon 5 of 12	1		ENSP00000480534.1
TYW1B	ENST00000610600.1	c.704G>A	p.Arg235Lys	missense_variant	Exon 6 of 8	2		ENSP00000484480.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461820 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 28, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.64
DANN	Benign	0.76
DEOGEN2	Benign	0.0025	.;T;.
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.51	T;T;T
M_CAP	Benign	0.00056	T
MetaRNN	Benign	0.11	T;T;T
PrimateAI	Benign	0.47	T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.18
MVP		0.34
GERP RS		1.7
Varity_R		0.041
gMVP		0.15

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: chr7-72242492;