rs41281938

Variant names:

• chr9-97472474-G-A
• rs41281938
• NM_014290.3:c.1923G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-97472474-G-A
• chr9-97472474-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_014290.3(TDRD7):​c.1923G>A​(p.Lys641Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0317 in 1,613,386 control chromosomes in the GnomAD database, including 1,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (198 hom., cov: 32)
  • Exomes 𝑓: 0.030 (872 hom.)
• Consequence: TDRD7 NM_014290.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.35
• Publications: 3 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 9-97472474-G-A is Benign according to our data. Variant chr9-97472474-G-A is described in ClinVar as Benign. ClinVar VariationId is 364071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD7	NM_014290.3	c.1923G>A	p.Lys641Lys	synonymous_variant	Exon 10 of 17	ENST00000355295.5	NP_055105.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD7	ENST00000355295.5	c.1923G>A	p.Lys641Lys	synonymous_variant	Exon 10 of 17	1	NM_014290.3	ENSP00000347444.4

Frequencies

GnomAD3 genomes AF: 0.0441 AC: 6702 AN: 152062 Hom.: 199 Cov.: 32

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0368

GnomAD2 exomes AF: 0.0288 AC: 7168 AN: 249128 AF XY: 0.0287

Gnomad AFR exome AF: 0.0938

Gnomad AMR exome AF: 0.0157

Gnomad ASJ exome AF: 0.0219

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0144

Gnomad NFE exome AF: 0.0304

Gnomad OTH exome AF: 0.0269

GnomAD4 exome AF: 0.0304 AC: 44417 AN: 1461206 Hom.: 872 Cov.: 31 AF XY: 0.0306 AC XY: 22212 AN XY: 726920

African (AFR) AF: 0.0918 AC: 3071 AN: 33448

American (AMR) AF: 0.0166 AC: 740 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 580 AN: 26124

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39662

South Asian (SAS) AF: 0.0349 AC: 3008 AN: 86248

European-Finnish (FIN) AF: 0.0140 AC: 746 AN: 53330

Middle Eastern (MID) AF: 0.0356 AC: 205 AN: 5764

European-Non Finnish (NFE) AF: 0.0308 AC: 34234 AN: 1111554

Other (OTH) AF: 0.0302 AC: 1825 AN: 60370

GnomAD4 genome AF: 0.0440 AC: 6701 AN: 152180 Hom.: 198 Cov.: 32 AF XY: 0.0424 AC XY: 3156 AN XY: 74416

African (AFR) AF: 0.0903 AC: 3747 AN: 41502

American (AMR) AF: 0.0262 AC: 400 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4818

European-Finnish (FIN) AF: 0.0134 AC: 142 AN: 10598

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0307 AC: 2090 AN: 68016

Other (OTH) AF: 0.0364 AC: 77 AN: 2116

Alfa AF: 0.0359 Hom.: 87

Bravo AF: 0.0464

Asia WGS AF: 0.0130 AC: 47 AN: 3478

EpiCase AF: 0.0309

EpiControl AF: 0.0294

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cataract 36 Benign:2

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:2

May 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.6
DANN	Benign	0.64
PhyloP100		1.3
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: rs41281938; hg19: chr9-100234756; COSMIC: COSV107439754;