1-151774486-C-T

Variant names:

• chr1-151774486-C-T
• rs768914173
• NM_001083965.2:c.1652G>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.1652G>A​(p.Gly551Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. G551A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TDRKH NM_001083965.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34
• Publications: 0 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=0.24826524).

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.1652G>A	p.Gly551Asp	missense	Exon 13 of 13	NP_001077434.1	Q9Y2W6-2
	TDRKH	NM_001083963.1		c.1652G>A	p.Gly551Asp	missense	Exon 13 of 13	NP_001077432.1	Q9Y2W6-2
	TDRKH	NM_006862.4		c.1652G>A	p.Gly551Asp	missense	Exon 13 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.1652G>A	p.Gly551Asp	missense	Exon 13 of 13	ENSP00000357815.3	Q9Y2W6-2
	TDRKH	ENST00000368827.10	TSL:1	c.1652G>A	p.Gly551Asp	missense	Exon 13 of 14	ENSP00000357819.6	Q9Y2W6-2
	TDRKH	ENST00000458431.6	TSL:1	c.1652G>A	p.Gly551Asp	missense	Exon 13 of 13	ENSP00000395718.2	Q9Y2W6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249334 AF XY: 0.00000739

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: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727238

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.87	T
Polyphen		1.0	D
Vest4		0.38
MutPred		0.21		Loss of glycosylation at S550 (P = 0.033)
MVP		0.41
MPC		1.1
ClinPred		0.81	D
GERP RS		5.5
Varity_R		0.40
gMVP		0.34
Mutation Taster		=83/17	polymorphism

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

dbSNP: rs768914173; hg19: chr1-151746962;