9-97428691-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014290.3(TDRD7):c.207+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00726 in 1,609,366 control chromosomes in the GnomAD database, including 369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (40 hom., cov: 33)
  • Exomes 𝑓: 0.0072 (329 hom.)
• Consequence: TDRD7 NM_014290.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.81

Genes affected

TDRD7 (HGNC:30831): (tudor domain containing 7) The protein encoded by this gene belongs to the Tudor family of proteins. This protein contains conserved Tudor domains and LOTUS domains. It is a component of RNA granules, which function in RNA processing. Mutations in this gene have been associated with cataract formation in mouse and human. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 9-97428691-G-A is Benign according to our data. Variant chr9-97428691-G-A is described in ClinVar as [Benign]. Clinvar id is 260380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD7	NM_014290.3	c.207+19G>A		intron_variant		ENST00000355295.5
TDRD7	NM_001302884.2	c.-15-2242G>A		intron_variant
TDRD7	XM_047423111.1	c.207+19G>A		intron_variant
TDRD7	XM_047423113.1	c.207+19G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD7	ENST00000355295.5	c.207+19G>A		intron_variant		1	NM_014290.3	P1

Frequencies

GnomAD3 genomes AF: 0.00792 AC: 1205 AN: 152168 Hom.: 40 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0426

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.0169 AC: 4204 AN: 248692 Hom.: 170 AF XY: 0.0177 AC XY: 2385 AN XY: 134620

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00666

Gnomad EAS exome AF: 0.109

Gnomad SAS exome AF: 0.0429

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.00239

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00719 AC: 10476 AN: 1457080 Hom.: 329 Cov.: 32 AF XY: 0.00824 AC XY: 5977 AN XY: 725088

Gnomad4 AFR exome AF: 0.000569

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.00774

Gnomad4 EAS exome AF: 0.0854

Gnomad4 SAS exome AF: 0.0433

Gnomad4 FIN exome AF: 0.0202

Gnomad4 NFE exome AF: 0.00118

Gnomad4 OTH exome AF: 0.0114

GnomAD4 genome AF: 0.00793 AC: 1208 AN: 152286 Hom.: 40 Cov.: 33 AF XY: 0.0101 AC XY: 754 AN XY: 74460

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0427

Gnomad4 FIN AF: 0.0246

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00262 Hom.: 5

Bravo AF: 0.00621

Asia WGS AF: 0.0600 AC: 207 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Cataract 36 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.24
Dann	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs16920147; hg19: chr9-100190973;