NM_004595.5:c.49+4152A>C

Variant names:

• chrX-21945025-A-C
• rs2238958
• NM_004595.5:c.49+4152A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004595.5(SMS):​c.49+4152A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 110,159 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
• Consequence: SMS NM_004595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMS	NM_004595.5	c.49+4152A>C		intron_variant	Intron 1 of 10	ENST00000404933.7	NP_004586.2
SMS	NM_001258423.2	c.49+4152A>C		intron_variant	Intron 1 of 8		NP_001245352.1
SMS	XM_011545568.3	c.-54+3658A>C		intron_variant	Intron 1 of 10		XP_011543870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMS	ENST00000404933.7	c.49+4152A>C		intron_variant	Intron 1 of 10	1	NM_004595.5	ENSP00000385746.2
SMS	ENST00000457085.2	c.394+3658A>C		intron_variant	Intron 1 of 5	5		ENSP00000407366.2
SMS	ENST00000379404.5	c.49+4152A>C		intron_variant	Intron 1 of 8	3		ENSP00000368714.1
SMS	ENST00000478094.1	n.96+4152A>C		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0000182 AC: 2 AN: 110159 Hom.: 0 Cov.: 22 AF XY: 0.0000308 AC XY: 1 AN XY: 32425

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000379

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000182 AC: 2 AN: 110159 Hom.: 0 Cov.: 22 AF XY: 0.0000308 AC XY: 1 AN XY: 32425

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000379

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000230 Hom.: 30238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.33
DANN	Benign	0.35

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

LitVar

Other links and lift over

dbSNP: rs2238958; hg19: chrX-21963143;