chr16-84130342-A-C

Variant names:

• chr16-84130342-A-C
• NM_031463.5:c.310T>G

Variant summary

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

The NM_031463.5(HSDL1):​c.310T>G​(p.Leu104Val) 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 pathogenic outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HSDL1 NM_031463.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0570
• 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, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSDL1	NM_031463.5	c.310T>G	p.Leu104Val	missense_variant	Exon 4 of 6	ENST00000219439.9	NP_113651.4
HSDL1	NM_001146051.2	c.310T>G	p.Leu104Val	missense_variant	Exon 4 of 7		NP_001139523.1
HSDL1	XM_005256189.4	c.310T>G	p.Leu104Val	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.310T>G	p.Leu104Val	missense_variant	Exon 4 of 6	1	NM_031463.5	ENSP00000219439.4
HSDL1	ENST00000434463.7	c.310T>G	p.Leu104Val	missense_variant	Exon 4 of 7	2		ENSP00000407437.3
HSDL1	ENST00000568857.5	c.310T>G	p.Leu104Val	missense_variant	Exon 4 of 4	4		ENSP00000457026.1
HSDL1	ENST00000562224.1	c.310T>G	p.Leu104Val	missense_variant	Exon 4 of 4	4		ENSP00000455797.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.310T>G (p.L104V) alteration is located in exon 4 (coding exon 2) of the HSDL1 gene. This alteration results from a T to G substitution at nucleotide position 310, causing the leucine (L) at amino acid position 104 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.8
DANN	Benign	0.94
DEOGEN2	Uncertain	0.59	D;.;D;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.71	T;T;D;D
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.9	M;M;.;.
PhyloP100		-0.057
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.4	N;N;D;D
REVEL	Benign	0.27
Sift	Benign	0.11	T;T;T;T
Sift4G	Uncertain	0.058	T;T;T;D
Polyphen		0.98	D;.;.;.
Vest4		0.36
MutPred		0.86		Loss of ubiquitination at K109 (P = 0.1278);Loss of ubiquitination at K109 (P = 0.1278);Loss of ubiquitination at K109 (P = 0.1278);Loss of ubiquitination at K109 (P = 0.1278);
MVP		0.44
MPC		0.14
ClinPred		0.36	T
GERP RS		-11
Varity_R		0.095
gMVP		0.76

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

hg19: chr16-84163947;