1-154547426-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182499.4(TDRD10):c.970G>A(p.Glu324Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: TDRD10 NM_182499.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.148

Genes affected

TDRD10 (HGNC:25316): (tudor domain containing 10) Predicted to enable RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07190323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD10	NM_182499.4	c.970G>A	p.Glu324Lys	missense_variant	12/13	ENST00000368482.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD10	ENST00000368482.8	c.970G>A	p.Glu324Lys	missense_variant	12/13	1	NM_182499.4	P1
TDRD10	ENST00000479937.5	n.715G>A		non_coding_transcript_exon_variant	7/8	1
TDRD10	ENST00000368480.3	c.970G>A	p.Glu324Lys	missense_variant	12/12	2
TDRD10	ENST00000468714.5	n.519G>A		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.970G>A (p.E324K) alteration is located in exon 12 (coding exon 11) of the TDRD10 gene. This alteration results from a G to A substitution at nucleotide position 970, causing the glutamic acid (E) at amino acid position 324 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	11
Dann	Benign	0.96
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.057
Sift	Benign	0.033	D;D
Polyphen		0.10	B;B
Vest4		0.13
MutPred		0.65		Gain of MoRF binding (P = 0.0023);Gain of MoRF binding (P = 0.0023);
MVP		0.088
MPC		0.42
ClinPred		0.060	T
GERP RS		2.5
Varity_R		0.029
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-154519902;