chr22-43829085-G-T

Variant names:

• chr22-43829085-G-T
• rs778676756
• NM_014351.4:c.717C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014351.4(SULT4A1):​c.717C>A​(p.Asn239Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,393,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N239N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SULT4A1 NM_014351.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.932
• Publications: 0 publications found

Genes affected

SULT4A1 (HGNC:14903): (sulfotransferase family 4A member 1) This gene encodes a member of the sulfotransferase family. The encoded protein is a brain-specific sulfotransferase believed to be involved in the metabolism of neurotransmitters. Polymorphisms in this gene may be associated with susceptibility to schizophrenia. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29651463).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014351.4. 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
	SULT4A1	NM_014351.4	MANE Select	c.717C>A	p.Asn239Lys	missense	Exon 6 of 7	NP_055166.1	Q9BR01-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT4A1	ENST00000330884.9	TSL:1 MANE Select	c.717C>A	p.Asn239Lys	missense	Exon 6 of 7	ENSP00000332565.4	Q9BR01-1
	SULT4A1	ENST00000422525.1	TSL:1	n.717C>A		non_coding_transcript_exon	Exon 6 of 8	ENSP00000388285.1	Q9BR01-2
	SULT4A1	ENST00000884819.1		c.378C>A	p.Asn126Lys	missense	Exon 3 of 4	ENSP00000554878.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000654 AC: 1 AN: 152790 AF XY: 0.0000124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1393340 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 686410

African (AFR) AF: 0.00 AC: 0 AN: 31382

American (AMR) AF: 0.00 AC: 0 AN: 35378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25004

East Asian (EAS) AF: 0.00 AC: 0 AN: 35342

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075302

Other (OTH) AF: 0.0000173 AC: 1 AN: 57750

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000251 Hom.: 0

ExAC AF: 0.00000908 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.93
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.091
Sift	Benign	0.083	T
Sift4G	Uncertain	0.010	D
Polyphen		0.56	P
Vest4		0.30
MutPred		0.66		Gain of methylation at N239 (P = 0.0081)
MVP		0.50
MPC		1.1
ClinPred		0.22	T
GERP RS		-3.5
Varity_R		0.65
gMVP		0.51
Mutation Taster		=30/70	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: rs778676756; hg19: chr22-44224965;