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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014290.3. 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
	TDRD7	NM_014290.3	MANE Select	c.1923G>A	p.Lys641Lys	synonymous	Exon 10 of 17	NP_055105.2
	TDRD7	NM_001302884.2		c.1701G>A	p.Lys567Lys	synonymous	Exon 9 of 16	NP_001289813.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD7	ENST00000355295.5	TSL:1 MANE Select	c.1923G>A	p.Lys641Lys	synonymous	Exon 10 of 17	ENSP00000347444.4
	TDRD7	ENST00000861598.1		c.1923G>A	p.Lys641Lys	synonymous	Exon 11 of 18	ENSP00000531657.1
	TDRD7	ENST00000861599.1		c.1911G>A	p.Lys637Lys	synonymous	Exon 10 of 17	ENSP00000531658.1

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Cataract 36 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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;