6-114057402-A-C

Variant names:

• chr6-114057402-A-C
• rs1209712418
• NM_153612.4:c.896T>G

Variant summary

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

The NM_153612.4(HS3ST5):​c.896T>G​(p.Ile299Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. I299T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HS3ST5 NM_153612.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.96
• Publications: 2 publications found

Genes affected

HS3ST5 (HGNC:19419): (heparan sulfate-glucosamine 3-sulfotransferase 5) HS3ST5 belongs to a group of heparan sulfate 3-O-sulfotransferases (EC 2.8.2.23) that transfer sulfate from 3-prime-phosphoadenosine 5-prime phosphosulfate (PAPS) to heparan sulfate and heparin (Mochizuki et al., 2003 [PubMed 12740361]).[supplied by OMIM, Mar 2008]

HDAC2-AS2 (HGNC:43590): (HDAC2 and HS3ST5 antisense RNA 2)

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=0.15922388).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153612.4. 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
	HS3ST5	NM_153612.4	MANE Select	c.896T>G	p.Ile299Ser	missense	Exon 5 of 5	NP_705840.2
	HS3ST5	NM_001387039.1		c.896T>G	p.Ile299Ser	missense	Exon 4 of 4	NP_001373968.1	Q8IZT8
	HS3ST5	NM_001387040.1		c.896T>G	p.Ile299Ser	missense	Exon 3 of 3	NP_001373969.1	Q8IZT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST5	ENST00000312719.10	TSL:2 MANE Select	c.896T>G	p.Ile299Ser	missense	Exon 5 of 5	ENSP00000427888.1	Q8IZT8
	HDAC2-AS2	ENST00000519104.5	TSL:1	n.1311-31535A>C		intron	N/A
	HS3ST5	ENST00000900060.1		c.896T>G	p.Ile299Ser	missense	Exon 6 of 6	ENSP00000570119.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.095
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	-0.81	N
PhyloP100		5.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	2.5	N
REVEL	Uncertain	0.38
Sift	Benign	0.72	T
Sift4G	Benign	0.78	T
Polyphen		0.52	P
Vest4		0.42
MutPred		0.44		Loss of stability (P = 0.0393)
MVP		0.42
MPC		0.53
ClinPred		0.91	D
GERP RS		5.9
Varity_R		0.17
gMVP		0.84
Mutation Taster		=39/61	disease causing

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: rs1209712418; hg19: chr6-114378566; COSMIC: COSV105891929;