16-84124668-G-T

Variant names:

• chr16-84124668-G-T
• rs997053743
• NM_031463.5:c.955C>A

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.955C>A​(p.Arg319Ser) 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. 15/22 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. R319C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSDL1 NM_031463.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 1 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=0.13945186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSDL1	NM_031463.5	c.955C>A	p.Arg319Ser	missense_variant	Exon 6 of 6	ENST00000219439.9	NP_113651.4
HSDL1	NM_001146051.2	c.790C>A	p.Arg264Ser	missense_variant	Exon 7 of 7		NP_001139523.1
HSDL1	XM_005256189.4	c.955C>A	p.Arg319Ser	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.955C>A	p.Arg319Ser	missense_variant	Exon 6 of 6	1	NM_031463.5	ENSP00000219439.4
HSDL1	ENST00000434463.7	c.790C>A	p.Arg264Ser	missense_variant	Exon 7 of 7	2		ENSP00000407437.3
HSDL1	ENST00000619773.1	n.537C>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461536 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111724

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.012
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.67	N;.
PhyloP100		2.7
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.93	N;N
REVEL	Benign	0.19
Sift	Benign	0.23	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0030	B;.
Vest4		0.17
MutPred		0.58		Loss of MoRF binding (P = 0.0129);.;
MVP		0.80
MPC		0.027
ClinPred		0.43	T
GERP RS		4.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.11
gMVP		0.69

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: rs997053743; hg19: chr16-84158273;