rs201135766

Variant names:

• chr1-151776184-C-T
• rs201135766
• NM_001083965.2:c.1129G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-151776184-C-T
• chr1-151776184-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001083965.2(TDRKH):​c.1129G>A​(p.Gly377Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000465 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G377D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: TDRKH NM_001083965.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.46
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.123211235).

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.1129G>A	p.Gly377Ser	missense	Exon 8 of 13	NP_001077434.1	Q9Y2W6-2
	TDRKH	NM_001083963.1		c.1129G>A	p.Gly377Ser	missense	Exon 8 of 13	NP_001077432.1	Q9Y2W6-2
	TDRKH	NM_006862.4		c.1129G>A	p.Gly377Ser	missense	Exon 8 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.1129G>A	p.Gly377Ser	missense	Exon 8 of 13	ENSP00000357815.3	Q9Y2W6-2
	TDRKH	ENST00000368827.10	TSL:1	c.1129G>A	p.Gly377Ser	missense	Exon 8 of 14	ENSP00000357819.6	Q9Y2W6-2
	TDRKH	ENST00000458431.6	TSL:1	c.1129G>A	p.Gly377Ser	missense	Exon 8 of 13	ENSP00000395718.2	Q9Y2W6-2

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000802 AC: 20 AN: 249484 AF XY: 0.0000443

Gnomad AFR exome AF: 0.000775

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000390 AC: 57 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.0000344 AC XY: 25 AN XY: 727244

African (AFR) AF: 0.000538 AC: 18 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 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: 0.0000232 AC: 2 AN: 86258

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

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1112008

Other (OTH) AF: 0.000132 AC: 8 AN: 60396

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74446

African (AFR) AF: 0.000361 AC: 15 AN: 41534

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000110 Hom.: 0

Bravo AF: 0.000193

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000522 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000108 AC: 13

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

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	0.28
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0059	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.5
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.097
Sift	Benign	0.23	T
Sift4G	Benign	0.34	T
Polyphen		0.47	P
Vest4		0.29
MVP		0.66
MPC		0.69
ClinPred		0.072	T
GERP RS		5.4
Varity_R		0.37
gMVP		0.36
Mutation Taster		=35/65	disease causing

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: rs201135766; hg19: chr1-151748660;