1-151775834-C-G

Variant names:

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

Variant summary

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

The NM_001083965.2(TDRKH):​c.1268G>C​(p.Arg423Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R423Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TDRKH NM_001083965.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>C	p.Arg423Pro	missense	Exon 9 of 13	NP_001077434.1	Q9Y2W6-2
	TDRKH	NM_001083963.1		c.1268G>C	p.Arg423Pro	missense	Exon 9 of 13	NP_001077432.1	Q9Y2W6-2
	TDRKH	NM_006862.4		c.1268G>C	p.Arg423Pro	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>C	p.Arg423Pro	missense	Exon 9 of 13	ENSP00000357815.3	Q9Y2W6-2
	TDRKH	ENST00000368827.10	TSL:1	c.1268G>C	p.Arg423Pro	missense	Exon 9 of 14	ENSP00000357819.6	Q9Y2W6-2
	TDRKH	ENST00000458431.6	TSL:1	c.1268G>C	p.Arg423Pro	missense	Exon 9 of 13	ENSP00000395718.2	Q9Y2W6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.91
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.18
Sift	Benign	0.11	T
Sift4G	Benign	0.076	T
Polyphen		0.52	P
Vest4		0.54
MutPred		0.59		Gain of glycosylation at R423 (P = 0.0531)
MVP		0.45
MPC		0.82
ClinPred		0.69	D
GERP RS		2.0
Varity_R		0.87
gMVP		0.78
Mutation Taster		=32/68	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;