rs6811863

Variant names:

• chr4-37960565-G-A
• rs6811863
• NM_006607.3:c.131G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-37960565-G-A
• chr4-37960565-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006607.3(PTTG2):​c.131G>A​(p.Arg44Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: PTTG2 NM_006607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 28 publications found

Genes affected

PTTG2 (HGNC:9691): (pituitary tumor-transforming 2) Predicted to enable SH3 domain binding activity. Predicted to be involved in homologous chromosome segregation and negative regulation of mitotic sister chromatid separation. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D1 (HGNC:11578): (TBC1 domain family member 1) TBC1D1 is the founding member of a family of proteins sharing a 180- to 200-amino acid TBC domain presumed to have a role in regulating cell growth and differentiation. These proteins share significant homology with TRE2 (USP6; MIM 604334), yeast Bub2, and CDC16 (MIM 603461) (White et al., 2000 [PubMed 10965142]).[supplied by OMIM, Mar 2008]

TBC1D1 Gene-Disease associations (from GenCC):

• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044691592).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006607.3. 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
	PTTG2	NM_006607.3	MANE Select	c.131G>A	p.Arg44Gln	missense	Exon 1 of 1	NP_006598.2	Q9NZH5-2
	TBC1D1	NM_001396959.1	MANE Select	c.418-53944G>A		intron	N/A	NP_001383888.1	A0A8V8TNS9
	TBC1D1	NM_015173.4		c.418-53944G>A		intron	N/A	NP_055988.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTTG2	ENST00000504686.2	TSL:6 MANE Select	c.131G>A	p.Arg44Gln	missense	Exon 1 of 1	ENSP00000424261.1	Q9NZH5-2
	TBC1D1	ENST00000698857.1	MANE Select	c.418-53944G>A		intron	N/A	ENSP00000513987.1	A0A8V8TNS9
	TBC1D1	ENST00000261439.9	TSL:1	c.418-53944G>A		intron	N/A	ENSP00000261439.4	Q86TI0-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151950 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250724 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461834 Hom.: 0 Cov.: 61 AF XY: 0.0000193 AC XY: 14 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111964

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151950 Hom.: 0 Cov.: 31 AF XY: 0.0000539 AC XY: 4 AN XY: 74216

African (AFR) AF: 0.00 AC: 0 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15260

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 14239

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.95
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00062	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.24
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.58	N
REVEL	Benign	0.032
Sift	Uncertain	0.011	D
Sift4G	Benign	0.18	T
Polyphen		0.0080	B
Vest4		0.056
MutPred		0.43		Loss of MoRF binding (P = 0.0161)
MVP		0.040
MPC		0.027
ClinPred		0.060	T
GERP RS		-4.0
PromoterAI		0.0012	Neutral
gMVP		0.068
Mutation Taster		=99/1	polymorphism

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: rs6811863; hg19: chr4-37962186;