22-30636887-T-C

Variant names:

• chr22-30636887-T-C
• rs763699549
• NM_001001479.4:c.437T>C

Variant summary

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

The NM_001001479.4(SLC35E4):​c.437T>C​(p.Phe146Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,612,550 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: SLC35E4 NM_001001479.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.57
• Publications: 0 publications found

Genes affected

SLC35E4 (HGNC:17058): (solute carrier family 35 member E4) Predicted to enable antiporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35E4	NM_001001479.4	c.437T>C	p.Phe146Ser	missense_variant	Exon 1 of 2	ENST00000343605.5	NP_001001479.1
SLC35E4	NM_001318370.2	c.437T>C	p.Phe146Ser	missense_variant	Exon 1 of 3		NP_001305299.1
SLC35E4	NM_001318371.2	c.437T>C	p.Phe146Ser	missense_variant	Exon 1 of 3		NP_001305300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35E4	ENST00000343605.5	c.437T>C	p.Phe146Ser	missense_variant	Exon 1 of 2	1	NM_001001479.4	ENSP00000339626.4
SLC35E4	ENST00000406566.1	c.437T>C	p.Phe146Ser	missense_variant	Exon 1 of 3	1		ENSP00000384377.1
SLC35E4	ENST00000451479.1	c.365T>C	p.Phe122Ser	missense_variant	Exon 1 of 3	1		ENSP00000413552.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152230 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000486 AC: 12 AN: 246660 AF XY: 0.0000597

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000656

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460320 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726442

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111488

Other (OTH) AF: 0.00 AC: 0 AN: 60300

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152230 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74382

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000577 AC: 3 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.437T>C (p.F146S) alteration is located in exon 1 (coding exon 1) of the SLC35E4 gene. This alteration results from a T to C substitution at nucleotide position 437, causing the phenylalanine (F) at amino acid position 146 to be replaced by a serine (S). 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	0.58
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.5	M;M;.
PhyloP100		5.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-6.6	D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.77	P;P;.
Vest4		0.46
MutPred		0.69		Gain of disorder (P = 0.0166);Gain of disorder (P = 0.0166);.;
MVP		0.68
MPC		0.76
ClinPred		0.45	T
GERP RS		5.2
PromoterAI		-0.017	Neutral
Varity_R		0.90
gMVP		0.81
Mutation Taster		=60/40	polymorphism

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: rs763699549; hg19: chr22-31032874;