NM_014351.4:c.415G>A

Variant names:

• chr22-43838960-C-T
• NM_014351.4:c.415G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014351.4(SULT4A1):​c.415G>A​(p.Val139Met) 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: 7.67
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768

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.415G>A	p.Val139Met	missense	Exon 4 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.415G>A	p.Val139Met	missense	Exon 4 of 7	ENSP00000332565.4	Q9BR01-1
	SULT4A1	ENST00000422525.1	TSL:1	n.415G>A		non_coding_transcript_exon	Exon 4 of 8	ENSP00000388285.1	Q9BR01-2
	SULT4A1	ENST00000884819.1		c.170-5226G>A		intron	N/A	ENSP00000554878.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	0.54	N
PhyloP100		7.7
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.29	N
REVEL	Uncertain	0.61
Sift	Benign	0.12	T
Sift4G	Benign	0.27	T
Polyphen		1.0	D
Vest4		0.67
MutPred		0.76		Gain of MoRF binding (P = 0.0797)
MVP		0.63
MPC		1.6
ClinPred		0.92	D
GERP RS		4.9
Varity_R		0.38
gMVP		0.74
Mutation Taster		=33/67	disease causing

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

Other links and lift over

hg19: chr22-44234840;