NM_001143936.2:c.5A>C

Variant names:

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

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>C​(p.Glu2Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C15orf61 NM_001143936.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.14094964).

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>C	p.Glu2Ala	missense	Exon 1 of 2	NP_001137408.1	A6NNL5
	IQCH-AS1	NR_040051.1		n.299+293T>G		intron	N/A
	IQCH-AS1	NR_040052.1		n.326+266T>G		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>C	p.Glu2Ala	missense	Exon 1 of 2	ENSP00000342254.4	A6NNL5
	IQCH-AS1	ENST00000561232.5	TSL:1	n.326+266T>G		intron	N/A
	IQCH-AS1	ENST00000559298.5	TSL:5	n.91+293T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.67	N
PhyloP100		1.6
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.063
Sift	Benign	0.070	T
Sift4G	Benign	0.15	T
Polyphen		0.034	B
Vest4		0.30
MutPred		0.17		Gain of methylation at R5 (P = 0.0446)
MVP		0.061
ClinPred		0.16	T
GERP RS		2.6
PromoterAI		0.40	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.13
gMVP		0.39

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;