chr1-151775834-C-T

Variant names:

• chr1-151775834-C-T
• rs372144473
• NM_001083965.2:c.1268G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001083965.2(TDRKH):​c.1268G>A​(p.Arg423Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: TDRKH NM_001083965.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.914
• Publications: 2 publications found

Genes affected

TDRKH (HGNC:11713): (tudor and KH domain containing) Predicted to enable RNA binding activity. Predicted to be involved in fertilization; gamete generation; and piRNA metabolic process. Predicted to be located in mitochondrion; pi-body; and piP-body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10103378).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083965.2. 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
	TDRKH	NM_001083965.2	MANE Select	c.1268G>A	p.Arg423Gln	missense	Exon 9 of 13	NP_001077434.1	Q9Y2W6-2
	TDRKH	NM_001083963.1		c.1268G>A	p.Arg423Gln	missense	Exon 9 of 13	NP_001077432.1	Q9Y2W6-2
	TDRKH	NM_006862.4		c.1268G>A	p.Arg423Gln	missense	Exon 9 of 14	NP_006853.2	Q9Y2W6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRKH	ENST00000368824.8	TSL:1 MANE Select	c.1268G>A	p.Arg423Gln	missense	Exon 9 of 13	ENSP00000357815.3	Q9Y2W6-2
	TDRKH	ENST00000368827.10	TSL:1	c.1268G>A	p.Arg423Gln	missense	Exon 9 of 14	ENSP00000357819.6	Q9Y2W6-2
	TDRKH	ENST00000458431.6	TSL:1	c.1268G>A	p.Arg423Gln	missense	Exon 9 of 13	ENSP00000395718.2	Q9Y2W6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249524 AF XY: 0.00

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461192 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 726748

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111436

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ESP6500AA AF: 0.000270 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000828 AC: 1

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	Benign	0.063
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	18
DANN	Benign	0.70
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.63
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.28	N
PhyloP100		0.91
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.033
Sift	Benign	0.35	T
Sift4G	Benign	0.19	T
Polyphen		0.016	B
Vest4		0.11
MVP		0.28
MPC		0.33
ClinPred		0.076	T
GERP RS		2.0
Varity_R		0.27
gMVP		0.24
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

dbSNP: rs372144473; hg19: chr1-151748310; COSMIC: COSV58617962; COSMIC: COSV58617962;