13-39042267-A-G

Variant names:

• chr13-39042267-A-G
• rs966518567
• NM_001012754.4:c.548A>G

Variant summary

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

The NM_001012754.4(NHLRC3):​c.548A>G​(p.Asp183Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,064 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D183V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NHLRC3 NM_001012754.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.29
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.548A>G	p.Asp183Gly	missense	Exon 4 of 7	NP_001012772.1	Q5JS37-1
	NHLRC3	NM_001017370.3		c.386-1823A>G		intron	N/A	NP_001017370.1	Q5JS37-2
	NHLRC3	NR_073109.1		n.619A>G		non_coding_transcript_exon	Exon 4 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHLRC3	ENST00000379600.8	TSL:1 MANE Select	c.548A>G	p.Asp183Gly	missense	Exon 4 of 7	ENSP00000368920.3	Q5JS37-1
	NHLRC3	ENST00000470258.5	TSL:1	c.-44A>G		5_prime_UTR	Exon 4 of 7	ENSP00000418127.1	C9J973
	NHLRC3	ENST00000379599.6	TSL:1	c.386-1823A>G		intron	N/A	ENSP00000368919.2	Q5JS37-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457064 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 725234

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.00 AC: 0 AN: 86154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107764

Other (OTH) AF: 0.0000166 AC: 1 AN: 60244

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.2	L
PhyloP100		9.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.36
Sift	Benign	0.23	T
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.46		Gain of catalytic residue at D183 (P = 0)
MVP		0.75
MPC		0.49
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.32
gMVP		0.85
Mutation Taster		=197/103	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs966518567; hg19: chr13-39616404;