NM_024719.4:c.341-1062G>C

Variant names:

• chr13-113352035-C-G
• rs755992
• NM_024719.4:c.341-1062G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024719.4(GRTP1):​c.341-1062G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 150,566 control chromosomes in the GnomAD database, including 9,247 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (9247 hom., cov: 28)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: GRTP1 NM_024719.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 4 publications found

Genes affected

GRTP1 (HGNC:20310): (growth hormone regulated TBC protein 1) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. [provided by Alliance of Genome Resources, Apr 2022]

GRTP1-AS1 (HGNC:39917): (GRTP1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRTP1	NM_024719.4	c.341-1062G>C		intron_variant	Intron 3 of 7	ENST00000375431.9	NP_078995.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRTP1	ENST00000375431.9	c.341-1062G>C		intron_variant	Intron 3 of 7	1	NM_024719.4	ENSP00000364580.3

Frequencies

GnomAD3 genomes AF: 0.339 AC: 50997 AN: 150460 Hom.: 9228 Cov.: 28

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.339 AC: 51067 AN: 150564 Hom.: 9247 Cov.: 28 AF XY: 0.340 AC XY: 24979 AN XY: 73426

African (AFR) AF: 0.406 AC: 16616 AN: 40970

American (AMR) AF: 0.421 AC: 6329 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3470

East Asian (EAS) AF: 0.599 AC: 3036 AN: 5072

South Asian (SAS) AF: 0.355 AC: 1701 AN: 4792

European-Finnish (FIN) AF: 0.244 AC: 2476 AN: 10140

Middle Eastern (MID) AF: 0.293 AC: 85 AN: 290

European-Non Finnish (NFE) AF: 0.284 AC: 19231 AN: 67790

Other (OTH) AF: 0.318 AC: 662 AN: 2084

Alfa AF: 0.165 Hom.: 313

Bravo AF: 0.363

Asia WGS AF: 0.471 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.44
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs755992; hg19: chr13-114006350; COSMIC: COSV58150006;