13-39038665-C-G

Variant names:

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

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>G​(p.Ala9Gly) 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. 16/22 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. A9V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NHLRC3 NM_001012754.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.10897148).

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>G	p.Ala9Gly	missense	Exon 1 of 7	NP_001012772.1	Q5JS37-1
	NHLRC3	NM_001017370.3		c.26C>G	p.Ala9Gly	missense	Exon 1 of 6	NP_001017370.1	Q5JS37-2
	NHLRC3	NR_073109.1		n.155+200C>G		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>G	p.Ala9Gly	missense	Exon 1 of 7	ENSP00000368920.3	Q5JS37-1
	NHLRC3	ENST00000379599.6	TSL:1	c.26C>G	p.Ala9Gly	missense	Exon 1 of 6	ENSP00000368919.2	Q5JS37-2
	NHLRC3	ENST00000470258.5	TSL:1	c.-508+200C>G		intron	N/A	ENSP00000418127.1	C9J973

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.11	N
PhyloP100		0.42
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.044
Sift	Benign	0.13	T
Sift4G	Benign	0.23	T
Polyphen		0.0030	B
Vest4		0.18
MutPred		0.62		Gain of catalytic residue at A9 (P = 0)
MVP		0.44
MPC		0.074
ClinPred		0.12	T
GERP RS		3.1
PromoterAI		-0.033	Neutral
Varity_R		0.067
gMVP		0.40
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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;