NM_001001795.2:c.511G>T

Variant names:

• chr8-144527482-C-A
• rs751107392
• NM_001001795.2:c.511G>T

Variant summary

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

The NM_001001795.2(C8orf82):​c.511G>T​(p.Ala171Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000904 in 1,106,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. A171T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: C8orf82 NM_001001795.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692
• Publications: 0 publications found

Genes affected

C8orf82 (HGNC:33826): (chromosome 8 open reading frame 82)

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=0.12066561).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001795.2. 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
	C8orf82	NM_001001795.2	MANE Select	c.511G>T	p.Ala171Ser	missense	Exon 3 of 3	NP_001001795.1	Q6P1X6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C8orf82	ENST00000524821.6	TSL:1 MANE Select	c.511G>T	p.Ala171Ser	missense	Exon 3 of 3	ENSP00000436621.1	Q6P1X6-1
	C8orf82	ENST00000313465.5	TSL:1	c.*486G>T		3_prime_UTR	Exon 2 of 2	ENSP00000316262.5	J3KNI2
	C8orf82	ENST00000532827.1	TSL:2	c.643G>T	p.Ala215Ser	missense	Exon 3 of 3	ENSP00000437092.1	H0YF29

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 9.04e-7 AC: 1 AN: 1106388 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 530878

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

African (AFR) AF: 0.00 AC: 0 AN: 21300

American (AMR) AF: 0.00 AC: 0 AN: 7246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13150

East Asian (EAS) AF: 0.00 AC: 0 AN: 21260

South Asian (SAS) AF: 0.00 AC: 0 AN: 39700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2878

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 932090

Other (OTH) AF: 0.0000230 AC: 1 AN: 43442

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.8
DANN	Benign	0.91
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.11	N
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.80	N
PhyloP100		0.69
PROVEAN	Benign	0.61	N
REVEL	Benign	0.015
Sift	Benign	0.69	T
Sift4G	Benign	0.62	T
Polyphen		0.027	B
Vest4		0.11
MutPred		0.38		Loss of helix (P = 0.0068)
MVP		0.014
MPC		0.99
ClinPred		0.14	T
GERP RS		0.47
PromoterAI		-0.036	Neutral
Varity_R		0.040
gMVP		0.35
Mutation Taster		=98/2	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: rs751107392; hg19: chr8-145752866;