Genetic Variant NM_004595.5:c.174T>C (chrX-21971900-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4BP7

The NM_004595.5(SMS):c.174T>C(p.Phe58Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.4e-7 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

SMS
NM_004595.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

4 publications found

Variant links:

Genes affected

SMS (HGNC:11123): (spermine synthase) This gene encodes a protein belonging to the spermidine/spermin synthase family and catalyzes the production of spermine from spermidine. Pseudogenes of this gene are located on chromosomes 1, 5, 6 and X. Mutations in this gene cause an X-linked intellectual disability called Snyder-Robinson Syndrome (SRS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

SMS Gene-Disease associations (from GenCC):

syndromic X-linked intellectual disability Snyder type
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

SMS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.216).

BP7

Synonymous conserved (PhyloP=1.41 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMS	NM_004595.5 link	c.174T>C	p.Phe58Phe	synonymous_variant	Exon 3 of 11	ENST00000404933.7	NP_004586.2	P52788-1
SMS	XM_005274582.3 link	c.72T>C	p.Phe24Phe	synonymous_variant	Exon 3 of 11		XP_005274639.1
SMS	XM_011545568.3 link	c.72T>C	p.Phe24Phe	synonymous_variant	Exon 3 of 11		XP_011543870.1
SMS	NM_001258423.2 link	c.170+4584T>C		intron_variant	Intron 2 of 8		NP_001245352.1	P52788-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMS	ENST00000404933.7 link	c.174T>C	p.Phe58Phe	synonymous_variant	Exon 3 of 11	1	NM_004595.5	ENSP00000385746.2	P52788-1
SMS	ENST00000457085.2 link	c.519T>C	p.Phe173Phe	synonymous_variant	Exon 3 of 6	5		ENSP00000407366.2	H7C2R7
SMS	ENST00000379404.5 link	c.170+4584T>C		intron_variant	Intron 2 of 8	3		ENSP00000368714.1	P52788-2
SMS	ENST00000478094.1 link	n.218-607T>C		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000546

AC:

AN:

183176

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

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

Data not reliable, filtered out with message: AS_VQSR

AF:

9.39e-7

AC:

AN:

1065116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

336370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25767

American (AMR)

AF:

0.0000284

AC:

AN:

35166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19170

East Asian (EAS)

AF:

0.00

AC:

AN:

30083

South Asian (SAS)

AF:

0.00

AC:

AN:

53361

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40523

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

812785

Other (OTH)

AF:

0.00

AC:

AN:

44975

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.3

(source)

DANN

Benign

0.72

PhyloP100

1.4

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over