NM_001012754.4:c.26C>T

Variant names:

• chr13-39038665-C-T
• rs998902595
• NM_001012754.4:c.26C>T

Variant summary

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

The NM_001012754.4(NHLRC3):​c.26C>T​(p.Ala9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: NHLRC3 NM_001012754.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.424
• Publications: 0 publications found

Genes affected

NHLRC3 (HGNC:33751): (NHL repeat containing 3) This gene encodes a protein containing NCL-1, HT2A and Lin-41 (NHL) family repeats. Mammalian NHL-repeat containing proteins may be involved in a variety of enzymatic processes, including protein modification through ubiquitination. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Aug 2012]

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=0.13375485).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012754.4. 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
	NHLRC3	NM_001012754.4	MANE Select	c.26C>T	p.Ala9Val	missense	Exon 1 of 7	NP_001012772.1	Q5JS37-1
	NHLRC3	NM_001017370.3		c.26C>T	p.Ala9Val	missense	Exon 1 of 6	NP_001017370.1	Q5JS37-2
	NHLRC3	NR_073109.1		n.155+200C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHLRC3	ENST00000379600.8	TSL:1 MANE Select	c.26C>T	p.Ala9Val	missense	Exon 1 of 7	ENSP00000368920.3	Q5JS37-1
	NHLRC3	ENST00000379599.6	TSL:1	c.26C>T	p.Ala9Val	missense	Exon 1 of 6	ENSP00000368919.2	Q5JS37-2
	NHLRC3	ENST00000470258.5	TSL:1	c.-508+200C>T		intron	N/A	ENSP00000418127.1	C9J973

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74336

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.42
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.044
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		0.062	B
Vest4		0.24
MutPred		0.62		Gain of catalytic residue at A11 (P = 0)
MVP		0.42
MPC		0.096
ClinPred		0.15	T
GERP RS		3.1
PromoterAI		0.025	Neutral
Varity_R		0.047
gMVP		0.42
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs998902595; hg19: chr13-39612802;