1-179595698-A-G

Variant names:

• chr1-179595698-A-G
• rs150798452
• NM_001199085.3:c.711A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001199085.3(TDRD5):​c.711A>G​(p.Pro237Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,613,762 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (10 hom.)
• Consequence: TDRD5 NM_001199085.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.656
• Publications: 2 publications found

Genes affected

TDRD5 (HGNC:20614): (tudor domain containing 5) Predicted to be involved in DNA methylation involved in gamete generation; P granule organization; and spermatid development. Predicted to be located in chromatoid body and pi-body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-179595698-A-G is Benign according to our data. Variant chr1-179595698-A-G is described in ClinVar as Benign. ClinVar VariationId is 709554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.656 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00611 (930/152326) while in subpopulation AFR AF = 0.0216 (897/41572). AF 95% confidence interval is 0.0204. There are 17 homozygotes in GnomAd4. There are 451 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199085.3. 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
	TDRD5	NM_001199085.3	MANE Select	c.711A>G	p.Pro237Pro	synonymous	Exon 4 of 18	NP_001186014.1	Q8NAT2-1
	TDRD5	NM_001199089.3		c.711A>G	p.Pro237Pro	synonymous	Exon 4 of 18	NP_001186018.1	Q8NAT2-1
	TDRD5	NM_001199091.2		c.711A>G	p.Pro237Pro	synonymous	Exon 4 of 17	NP_001186020.1	Q8NAT2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD5	ENST00000444136.6	TSL:1 MANE Select	c.711A>G	p.Pro237Pro	synonymous	Exon 4 of 18	ENSP00000406052.1	Q8NAT2-1
	TDRD5	ENST00000294848.12	TSL:1	c.711A>G	p.Pro237Pro	synonymous	Exon 4 of 17	ENSP00000294848.8	Q8NAT2-3
	TDRD5	ENST00000367614.5	TSL:2	c.711A>G	p.Pro237Pro	synonymous	Exon 4 of 17	ENSP00000356586.1	Q8NAT2-3

Frequencies

GnomAD3 genomes AF: 0.00613 AC: 933 AN: 152208 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00175 AC: 438 AN: 250812 AF XY: 0.00125

Gnomad AFR exome AF: 0.0242

Gnomad AMR exome AF: 0.000991

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000639 AC: 934 AN: 1461436 Hom.: 10 Cov.: 30 AF XY: 0.000549 AC XY: 399 AN XY: 727026

African (AFR) AF: 0.0218 AC: 728 AN: 33458

American (AMR) AF: 0.00105 AC: 47 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111804

Other (OTH) AF: 0.00146 AC: 88 AN: 60376

GnomAD4 genome AF: 0.00611 AC: 930 AN: 152326 Hom.: 17 Cov.: 32 AF XY: 0.00606 AC XY: 451 AN XY: 74474

African (AFR) AF: 0.0216 AC: 897 AN: 41572

American (AMR) AF: 0.00150 AC: 23 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00321 Hom.: 5

Bravo AF: 0.00672

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.61
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs150798452; hg19: chr1-179564833;