rs40941

Variant names:

• chr7-108562481-C-T
• rs40941
• NM_001130475.3:c.*1710G>A

Variant summary

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

The NM_001130475.3(THAP5):​c.*1710G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,010 control chromosomes in the GnomAD database, including 6,793 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 0.29 (6793 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: THAP5 NM_001130475.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 14 publications found

Genes affected

THAP5 (HGNC:23188): (THAP domain containing 5) Enables protease binding activity. Involved in negative regulation of cell cycle and negative regulation of transcription by RNA polymerase II. Located in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PNPLA8 (HGNC:28900): (patatin like phospholipase domain containing 8) This gene encodes a member of the patatin-like phospholipase domain containing protein family. Members of this family are phospholipases which catalyze the cleavage of fatty acids from membrane phospholipids. The product of this gene is a calcium-independent phospholipase. Mutations in this gene have been associated with mitochondrial myopathy with lactic acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2015]

PNPLA8 Gene-Disease associations (from GenCC):

• mitochondrial myopathy-lactic acidosis-deafness syndrome

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP5	NM_001130475.3	c.*1710G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000415914.4	NP_001123947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THAP5	ENST00000415914.4	c.*1710G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_001130475.3	ENSP00000400500.2
THAP5	ENST00000468884.1	n.108+7009G>A		intron_variant	Intron 1 of 1	3
PNPLA8	ENST00000489738.1	n.177+7009G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44193 AN: 151890 Hom.: 6793 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.268

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

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) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.291 AC: 44193 AN: 152008 Hom.: 6793 Cov.: 32 AF XY: 0.283 AC XY: 21048 AN XY: 74286

African (AFR) AF: 0.281 AC: 11631 AN: 41438

American (AMR) AF: 0.242 AC: 3695 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 748 AN: 3468

East Asian (EAS) AF: 0.0669 AC: 347 AN: 5188

South Asian (SAS) AF: 0.161 AC: 775 AN: 4820

European-Finnish (FIN) AF: 0.300 AC: 3158 AN: 10544

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22989 AN: 67958

Other (OTH) AF: 0.264 AC: 558 AN: 2110

Alfa AF: 0.310 Hom.: 1332

Bravo AF: 0.285

Asia WGS AF: 0.121 AC: 420 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.57
PhyloP100		-0.050
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: rs40941; hg19: chr7-108202925;