chr3-186554367-C-T

Variant names:

• chr3-186554367-C-T
• rs61732808
• NM_018138.5:c.1431G>A

Variant summary

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

The NM_018138.5(TBCCD1):​c.1431G>A​(p.Gly477Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,614,126 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (100 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (97 hom.)
• Consequence: TBCCD1 NM_018138.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.26
• Publications: 2 publications found

Genes affected

TBCCD1 (HGNC:25546): (TBCC domain containing 1) Involved in several processes, including maintenance of Golgi location; maintenance of centrosome location; and regulation of cell shape. Located in spindle pole centrosome. [provided by Alliance of Genome Resources, Apr 2022]

TBCCD1 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 3-186554367-C-T is Benign according to our data. Variant chr3-186554367-C-T is described in ClinVar as Benign. ClinVar VariationId is 781974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018138.5. 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
	TBCCD1	NM_018138.5	MANE Select	c.1431G>A	p.Gly477Gly	synonymous	Exon 6 of 8	NP_060608.1	Q9NVR7-1
	TBCCD1	NM_001134415.1		c.1431G>A	p.Gly477Gly	synonymous	Exon 6 of 8	NP_001127887.1	Q9NVR7-1
	TBCCD1	NM_001286749.2		c.1143G>A	p.Gly381Gly	synonymous	Exon 5 of 7	NP_001273678.1	Q9NVR7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCCD1	ENST00000338733.10	TSL:1 MANE Select	c.1431G>A	p.Gly477Gly	synonymous	Exon 6 of 8	ENSP00000341652.5	Q9NVR7-1
	TBCCD1	ENST00000424280.5	TSL:5	c.1431G>A	p.Gly477Gly	synonymous	Exon 6 of 8	ENSP00000411253.1	Q9NVR7-1
	TBCCD1	ENST00000894072.1		c.1431G>A	p.Gly477Gly	synonymous	Exon 6 of 8	ENSP00000564131.1

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2985 AN: 152116 Hom.: 97 Cov.: 32

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0125

GnomAD2 exomes AF: 0.00563 AC: 1415 AN: 251410 AF XY: 0.00408

Gnomad AFR exome AF: 0.0696

Gnomad AMR exome AF: 0.00593

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000281

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00229 AC: 3346 AN: 1461892 Hom.: 97 Cov.: 32 AF XY: 0.00199 AC XY: 1445 AN XY: 727246

African (AFR) AF: 0.0741 AC: 2481 AN: 33480

American (AMR) AF: 0.00664 AC: 297 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00203 AC: 53 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5768

European-Non Finnish (NFE) AF: 0.000156 AC: 174 AN: 1112012

Other (OTH) AF: 0.00503 AC: 304 AN: 60396

GnomAD4 genome AF: 0.0197 AC: 3006 AN: 152234 Hom.: 100 Cov.: 32 AF XY: 0.0187 AC XY: 1395 AN XY: 74420

African (AFR) AF: 0.0683 AC: 2838 AN: 41528

American (AMR) AF: 0.00706 AC: 108 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68030

Other (OTH) AF: 0.0123 AC: 26 AN: 2110

Alfa AF: 0.0102 Hom.: 32

Bravo AF: 0.0228

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000474

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	-0.34
CADD	Benign	13
DANN	Benign	0.66
PhyloP100		1.3
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs61732808; hg19: chr3-186272156;