NM_001011719.2:c.641G>A

Variant names:

• chrX-3015270-G-A
• rs61995728
• NM_001011719.2:c.641G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001011719.2(ARSH):​c.641G>A​(p.Ser214Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00681 in 1,209,268 control chromosomes in the GnomAD database, including 330 homozygotes. There are 2,235 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (171 hom., 1056 hem., cov: 22)
  • Exomes 𝑓: 0.0039 (159 hom. 1179 hem.)
• Consequence: ARSH NM_001011719.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.10
• Publications: 1 publications found

Genes affected

ARSH (HGNC:32488): (arylsulfatase family member H) Sulfatases, such as ARSH, hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules (Sardiello et al., 2005 [PubMed 16174644]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023491979).
• BP6: Variant X-3015270-G-A is Benign according to our data. Variant chrX-3015270-G-A is described in ClinVar as Benign. ClinVar VariationId is 558983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011719.2. 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
	ARSH	NM_001011719.2	MANE Select	c.641G>A	p.Ser214Asn	missense	Exon 4 of 9	NP_001011719.1	Q5FYA8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSH	ENST00000381130.3	TSL:1 MANE Select	c.641G>A	p.Ser214Asn	missense	Exon 4 of 9	ENSP00000370522.3	Q5FYA8

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 3947 AN: 111209 Hom.: 172 Cov.: 22

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0204

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000379

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.000414

Gnomad OTH AF: 0.0301

GnomAD2 exomes AF: 0.0103 AC: 1886 AN: 182722 AF XY: 0.00638

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.00752

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000589

Gnomad OTH exome AF: 0.00509

GnomAD4 exome AF: 0.00390 AC: 4279 AN: 1098006 Hom.: 159 Cov.: 31 AF XY: 0.00324 AC XY: 1179 AN XY: 363366

African (AFR) AF: 0.123 AC: 3250 AN: 26398

American (AMR) AF: 0.00898 AC: 316 AN: 35200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.000259 AC: 14 AN: 54096

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40516

Middle Eastern (MID) AF: 0.00943 AC: 39 AN: 4137

European-Non Finnish (NFE) AF: 0.000272 AC: 229 AN: 841991

Other (OTH) AF: 0.00933 AC: 430 AN: 46084

GnomAD4 genome AF: 0.0355 AC: 3952 AN: 111262 Hom.: 171 Cov.: 22 AF XY: 0.0315 AC XY: 1056 AN XY: 33498

African (AFR) AF: 0.121 AC: 3699 AN: 30514

American (AMR) AF: 0.0164 AC: 170 AN: 10384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3546

South Asian (SAS) AF: 0.000381 AC: 1 AN: 2625

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6010

Middle Eastern (MID) AF: 0.00461 AC: 1 AN: 217

European-Non Finnish (NFE) AF: 0.000414 AC: 22 AN: 53121

Other (OTH) AF: 0.0297 AC: 45 AN: 1516

Alfa AF: 0.0118 Hom.: 565

Bravo AF: 0.0411

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000692 AC: 2

ESP6500AA AF: 0.128 AC: 491

ESP6500EA AF: 0.000892 AC: 6

ExAC AF: 0.0114 AC: 1382

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Uncertain	0.55	D
FATHMM_MKL	Benign	0.086	N
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.88	L
PhyloP100		2.1
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.38
Sift	Benign	0.31	T
Sift4G	Benign	0.31	T
Polyphen		0.97	D
Vest4		0.091
MPC		0.58
ClinPred		0.049	T
GERP RS		4.0
Varity_R		0.28
gMVP		0.86
Mutation Taster		=99/1	polymorphism (auto)

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: rs61995728; hg19: chrX-2933311;