chr16-84124680-T-C

Variant names:

• chr16-84124680-T-C
• rs2086585357
• NM_031463.5:c.943A>G

Variant summary

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

The NM_031463.5(HSDL1):​c.943A>G​(p.Asn315Asp) 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. 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: 32)
• Consequence: HSDL1 NM_031463.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20508382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSDL1	NM_031463.5	c.943A>G	p.Asn315Asp	missense_variant	Exon 6 of 6	ENST00000219439.9	NP_113651.4
HSDL1	NM_001146051.2	c.778A>G	p.Asn260Asp	missense_variant	Exon 7 of 7		NP_001139523.1
HSDL1	XM_005256189.4	c.943A>G	p.Asn315Asp	missense_variant	Exon 6 of 6		XP_005256246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSDL1	ENST00000219439.9	c.943A>G	p.Asn315Asp	missense_variant	Exon 6 of 6	1	NM_031463.5	ENSP00000219439.4
HSDL1	ENST00000434463.7	c.778A>G	p.Asn260Asp	missense_variant	Exon 7 of 7	2		ENSP00000407437.3
HSDL1	ENST00000619773.1	n.525A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.943A>G (p.N315D) alteration is located in exon 6 (coding exon 4) of the HSDL1 gene. This alteration results from a A to G substitution at nucleotide position 943, causing the asparagine (N) at amino acid position 315 to be replaced by an aspartic acid (D). 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	0.10
BayesDel_addAF	Benign	0.0097	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T;.
Eigen	Benign	-0.082
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.73	T;T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.0	M;.
PhyloP100		1.8
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.18
Sift	Benign	0.61	T;T
Sift4G	Benign	0.63	T;T
Polyphen		0.19	B;.
Vest4		0.32
MutPred		0.53		Loss of MoRF binding (P = 0.0346);.;
MVP		0.79
MPC		0.027
ClinPred		0.48	T
GERP RS		5.6
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.065
gMVP		0.66

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

dbSNP: rs2086585357; hg19: chr16-84158285;