16-84130153-C-G

Variant names:

• chr16-84130153-C-G
• rs1016180601
• NM_031463.5:c.499G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031463.5(HSDL1):​c.499G>C​(p.Glu167Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. E167K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSDL1 NM_031463.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.42
• Publications: 0 publications found

Genes affected

HSDL1 (HGNC:16475): (hydroxysteroid dehydrogenase like 1) Predicted to enable oxidoreductase activity. Located in intermediate filament cytoskeleton and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSDL1	NM_031463.5	c.499G>C	p.Glu167Gln	missense_variant	Exon 4 of 6	ENST00000219439.9	NP_113651.4
HSDL1	NM_001146051.2	c.334G>C	p.Glu112Gln	missense_variant	Exon 5 of 7		NP_001139523.1
HSDL1	XM_005256189.4	c.499G>C	p.Glu167Gln	missense_variant	Exon 4 of 6		XP_005256246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSDL1	ENST00000219439.9	c.499G>C	p.Glu167Gln	missense_variant	Exon 4 of 6	1	NM_031463.5	ENSP00000219439.4
HSDL1	ENST00000434463.7	c.334G>C	p.Glu112Gln	missense_variant	Exon 5 of 7	2		ENSP00000407437.3
HSDL1	ENST00000568857.5	c.*166G>C		downstream_gene_variant		4		ENSP00000457026.1
HSDL1	ENST00000562224.1	c.*175G>C		downstream_gene_variant		4		ENSP00000455797.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251494 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Uncertain	0.47	D
MutationAssessor	Benign	2.0	M;.
PhyloP100		7.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.55
Sift	Benign	0.056	T;T
Sift4G	Benign	0.080	T;T
Polyphen		0.76	P;.
Vest4		0.73
MutPred		0.43		Loss of ubiquitination at K169 (P = 0.0661);.;
MVP		0.92
MPC		0.14
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.25
gMVP		0.75

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: rs1016180601; hg19: chr16-84163758;