rs777031702

Variant names:

• chr4-26673883-C-A
• rs777031702
• NM_018317.4:c.811C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-26673883-C-A
• chr4-26673883-C-G
• chr4-26673883-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018317.4(TBC1D19):​c.811C>A​(p.Pro271Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000021 in 1,431,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P271S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TBC1D19 NM_018317.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.24
• Publications: 1 publications found

Genes affected

TBC1D19 (HGNC:25624): (TBC1 domain family member 19) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19452795).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018317.4. 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
	TBC1D19	NM_018317.4	MANE Select	c.811C>A	p.Pro271Thr	missense	Exon 11 of 21	NP_060787.2	Q8N5T2-1
	TBC1D19	NM_001292054.2		c.616C>A	p.Pro206Thr	missense	Exon 8 of 18	NP_001278983.1	Q8N5T2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D19	ENST00000264866.9	TSL:1 MANE Select	c.811C>A	p.Pro271Thr	missense	Exon 11 of 21	ENSP00000264866.4	Q8N5T2-1
	TBC1D19	ENST00000511789.5	TSL:1	c.616C>A	p.Pro206Thr	missense	Exon 8 of 18	ENSP00000425569.1	Q8N5T2-2
	TBC1D19	ENST00000502873.5	TSL:1	n.921C>A		non_coding_transcript_exon	Exon 11 of 20

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1431254 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 711190

African (AFR) AF: 0.0000618 AC: 2 AN: 32338

American (AMR) AF: 0.00 AC: 0 AN: 41978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25220

East Asian (EAS) AF: 0.00 AC: 0 AN: 38884

South Asian (SAS) AF: 0.00 AC: 0 AN: 82148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093384

Other (OTH) AF: 0.0000170 AC: 1 AN: 58956

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000254 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	0.0061	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.038	T
Eigen	Benign	0.088
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.14
Sift	Benign	0.46	T
Sift4G	Benign	0.63	T
Polyphen		0.51	P
Vest4		0.47
MutPred		0.40		Gain of helix (P = 0.0893)
MVP		0.57
MPC		0.37
ClinPred		0.58	D
GERP RS		5.2
Varity_R		0.25
gMVP		0.29
Mutation Taster		=46/54	disease causing

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: rs777031702; hg19: chr4-26675505;