NM_004837.4:c.142-6dupT

Variant names:

• chr1-235341998-A-AT
• rs3841735
• NM_004837.4:c.142-6dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004837.4(GGPS1):​c.142-6dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,463,350 control chromosomes in the GnomAD database, including 89,021 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8231 hom., cov: 0)
  • Exomes 𝑓: 0.35 (80790 hom.)
• Consequence: GGPS1 NM_004837.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• Publications: 8 publications found

Genes affected

GGPS1 (HGNC:4249): (geranylgeranyl diphosphate synthase 1) This gene is a member of the prenyltransferase family and encodes a protein with geranylgeranyl diphosphate (GGPP) synthase activity. The enzyme catalyzes the synthesis of GGPP from farnesyl diphosphate and isopentenyl diphosphate. GGPP is an important molecule responsible for the C20-prenylation of proteins and for the regulation of a nuclear hormone receptor. Alternate transcriptional splice variants, both protein-coding and non-protein-coding, have been found for this gene. [provided by RefSeq, Sep 2010]

GGPS1 Gene-Disease associations (from GenCC):

• muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000285053 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGPS1	NM_004837.4	c.142-6dupT		splice_region_variant, intron_variant	Intron 3 of 3	ENST00000282841.9	NP_004828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGPS1	ENST00000282841.9	c.142-13_142-12insT		intron_variant	Intron 3 of 3	1	NM_004837.4	ENSP00000282841.5
ENSG00000285053	ENST00000647186.1	c.-435+6664_-435+6665insT		intron_variant	Intron 2 of 18			ENSP00000494775.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48836 AN: 151818 Hom.: 8217 Cov.: 0

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.341 AC: 64550 AN: 189418 AF XY: 0.348

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.281

Gnomad EAS exome AF: 0.228

Gnomad FIN exome AF: 0.370

Gnomad NFE exome AF: 0.335

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.345 AC: 452814 AN: 1311414 Hom.: 80790 Cov.: 21 AF XY: 0.351 AC XY: 229181 AN XY: 653020

African (AFR) AF: 0.241 AC: 6968 AN: 28910

American (AMR) AF: 0.330 AC: 10403 AN: 31494

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 6300 AN: 22196

East Asian (EAS) AF: 0.261 AC: 10045 AN: 38540

South Asian (SAS) AF: 0.515 AC: 37423 AN: 72642

European-Finnish (FIN) AF: 0.374 AC: 18975 AN: 50732

Middle Eastern (MID) AF: 0.309 AC: 1636 AN: 5302

European-Non Finnish (NFE) AF: 0.340 AC: 342627 AN: 1006950

Other (OTH) AF: 0.337 AC: 18437 AN: 54648

GnomAD4 genome AF: 0.322 AC: 48878 AN: 151936 Hom.: 8231 Cov.: 0 AF XY: 0.328 AC XY: 24373 AN XY: 74254

African (AFR) AF: 0.260 AC: 10784 AN: 41432

American (AMR) AF: 0.323 AC: 4924 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 997 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1182 AN: 5170

South Asian (SAS) AF: 0.525 AC: 2522 AN: 4800

European-Finnish (FIN) AF: 0.374 AC: 3940 AN: 10540

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23586 AN: 67956

Other (OTH) AF: 0.301 AC: 635 AN: 2110

Alfa AF: 0.227 Hom.: 777

Asia WGS AF: 0.362 AC: 1255 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs3841735; hg19: chr1-235505313; COSMIC: COSV51397079; COSMIC: COSV51397079;