NM_014351.4:c.784A>C

Variant names:

• chr22-43826072-T-G
• NM_014351.4:c.784A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014351.4(SULT4A1):​c.784A>C​(p.Asn262His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SULT4A1 NM_014351.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.84

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.883

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT4A1	NM_014351.4	c.784A>C	p.Asn262His	missense_variant	Exon 7 of 7	ENST00000330884.9	NP_055166.1
SULT4A1	XM_011530121.2	c.445A>C	p.Asn149His	missense_variant	Exon 4 of 4		XP_011528423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT4A1	ENST00000330884.9	c.784A>C	p.Asn262His	missense_variant	Exon 7 of 7	1	NM_014351.4	ENSP00000332565.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.784A>C (p.N262H) alteration is located in exon 7 (coding exon 7) of the SULT4A1 gene. This alteration results from a A to C substitution at nucleotide position 784, causing the asparagine (N) at amino acid position 262 to be replaced by a histidine (H). 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	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.60		Gain of methylation at K264 (P = 0.0905);
MVP		0.86
MPC		2.2
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.73
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-44221952;