rs16920147

Variant names:

• chr9-97428691-G-A
• rs16920147
• NM_014290.3:c.207+19G>A

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -2.81
• Publications: 1 publications found

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]

TDRD7 Gene-Disease associations (from GenCC):

• cataract 36

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TDRD7	NM_014290.3	c.207+19G>A		intron_variant	Intron 2 of 16	ENST00000355295.5	NP_055105.2
TDRD7	NM_001302884.2	c.-15-2242G>A		intron_variant	Intron 1 of 15		NP_001289813.1
TDRD7	XM_047423111.1	c.207+19G>A		intron_variant	Intron 2 of 16		XP_047279067.1
TDRD7	XM_047423113.1	c.207+19G>A		intron_variant	Intron 2 of 13		XP_047279069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD7	ENST00000355295.5	c.207+19G>A		intron_variant	Intron 2 of 16	1	NM_014290.3	ENSP00000347444.4

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

GnomAD2 exomes AF: 0.0169 AC: 4204 AN: 248692 AF XY: 0.0177

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 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

African (AFR) AF: 0.000569 AC: 19 AN: 33384

American (AMR) AF: 0.00190 AC: 85 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00774 AC: 202 AN: 26108

East Asian (EAS) AF: 0.0854 AC: 3389 AN: 39676

South Asian (SAS) AF: 0.0433 AC: 3732 AN: 86192

European-Finnish (FIN) AF: 0.0202 AC: 1035 AN: 51330

Middle Eastern (MID) AF: 0.00284 AC: 16 AN: 5634

European-Non Finnish (NFE) AF: 0.00118 AC: 1308 AN: 1109822

Other (OTH) AF: 0.0114 AC: 690 AN: 60264

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

African (AFR) AF: 0.000794 AC: 33 AN: 41562

American (AMR) AF: 0.00196 AC: 30 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00894 AC: 31 AN: 3468

East Asian (EAS) AF: 0.104 AC: 539 AN: 5184

South Asian (SAS) AF: 0.0427 AC: 206 AN: 4830

European-Finnish (FIN) AF: 0.0246 AC: 261 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00138 AC: 94 AN: 68030

Other (OTH) AF: 0.00664 AC: 14 AN: 2108

Alfa AF: 0.00250 Hom.: 5

Bravo AF: 0.00621

Asia WGS AF: 0.0600 AC: 207 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 23, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cataract 36 Benign:1

Jan 19, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.24
DANN	Benign	0.84
PhyloP100		-2.8
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: rs16920147; hg19: chr9-100190973; COSMIC: COSV107439862;