NM_014351.4:c.784A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_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

Scores

7
11
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84
Variant links:
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]

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ACMG classification

Classification made for transcript

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
SULT4A1NM_014351.4 linkc.784A>C p.Asn262His missense_variant Exon 7 of 7 ENST00000330884.9 NP_055166.1 Q9BR01-1
SULT4A1XM_011530121.2 linkc.445A>C p.Asn149His missense_variant Exon 4 of 4 XP_011528423.1 B7Z2E1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SULT4A1ENST00000330884.9 linkc.784A>C p.Asn262His missense_variant Exon 7 of 7 1 NM_014351.4 ENSP00000332565.4 Q9BR01-1

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
LINK: link

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; API