1-151789328-A-G

Variant names:

• chr1-151789328-A-G
• rs868866
• NM_001083965.2:c.-28+1052T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083965.2(TDRKH):​c.-28+1052T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,148 control chromosomes in the GnomAD database, including 13,495 homozygotes. 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: 𝑓 0.41 (13495 hom., cov: 33)
• Consequence: TDRKH NM_001083965.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRKH	NM_001083965.2	MANE Select	c.-28+1052T>C		intron	N/A	NP_001077434.1
	TDRKH	NM_001083963.1		c.-28+1077T>C		intron	N/A	NP_001077432.1
	TDRKH	NM_006862.4		c.-28+1052T>C		intron	N/A	NP_006853.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRKH	ENST00000368824.8	TSL:1 MANE Select	c.-28+1052T>C		intron	N/A	ENSP00000357815.3
	TDRKH	ENST00000368827.10	TSL:1	c.-28+1052T>C		intron	N/A	ENSP00000357819.6
	TDRKH	ENST00000458431.6	TSL:1	c.-28+1077T>C		intron	N/A	ENSP00000395718.2

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61881 AN: 152030 Hom.: 13495 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.405

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.407 AC: 61885 AN: 152148 Hom.: 13495 Cov.: 33 AF XY: 0.401 AC XY: 29795 AN XY: 74364

African (AFR) AF: 0.292 AC: 12108 AN: 41492

American (AMR) AF: 0.326 AC: 4987 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1395 AN: 3468

East Asian (EAS) AF: 0.219 AC: 1137 AN: 5194

South Asian (SAS) AF: 0.397 AC: 1919 AN: 4828

European-Finnish (FIN) AF: 0.468 AC: 4944 AN: 10558

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.499 AC: 33939 AN: 68006

Other (OTH) AF: 0.406 AC: 855 AN: 2106

Alfa AF: 0.361 Hom.: 1609

Bravo AF: 0.389

Asia WGS AF: 0.339 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.2
DANN	Benign	0.62
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs868866; hg19: chr1-151761804;