15-67521253-A-G

Variant names:

• chr15-67521253-A-G
• rs2084157262
• NM_001143936.2:c.5A>G

Variant summary

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

The NM_001143936.2(C15orf61):​c.5A>G​(p.Glu2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000267 in 1,124,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. E2A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: C15orf61 NM_001143936.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 0 publications found

Genes affected

C15orf61 (HGNC:34453): (chromosome 15 open reading frame 61) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

IQCH-AS1 (HGNC:44104): (IQCH antisense RNA 1)

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=0.1640018).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143936.2. 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
	C15orf61	NM_001143936.2	MANE Select	c.5A>G	p.Glu2Gly	missense	Exon 1 of 2	NP_001137408.1	A6NNL5
	IQCH-AS1	NR_040051.1		n.299+293T>C		intron	N/A
	IQCH-AS1	NR_040052.1		n.326+266T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C15orf61	ENST00000342683.6	TSL:1 MANE Select	c.5A>G	p.Glu2Gly	missense	Exon 1 of 2	ENSP00000342254.4	A6NNL5
	IQCH-AS1	ENST00000561232.5	TSL:1	n.326+266T>C		intron	N/A
	IQCH-AS1	ENST00000559298.5	TSL:5	n.91+293T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000267 AC: 3 AN: 1124212 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 537252

African (AFR) AF: 0.00 AC: 0 AN: 23254

American (AMR) AF: 0.00 AC: 0 AN: 9292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15108

East Asian (EAS) AF: 0.0000376 AC: 1 AN: 26572

South Asian (SAS) AF: 0.00 AC: 0 AN: 34704

European-Finnish (FIN) AF: 0.0000822 AC: 2 AN: 24338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3112

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 942408

Other (OTH) AF: 0.00 AC: 0 AN: 45424

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.65
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.6
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.058
Sift	Uncertain	0.028	D
Sift4G	Benign	0.064	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.24		Gain of loop (P = 0.0045)
MVP		0.25
ClinPred		0.37	T
GERP RS		2.6
PromoterAI		-0.30	Neutral
Varity_R		0.20
gMVP		0.39
Mutation Taster		=82/18	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: rs2084157262; hg19: chr15-67813591;