rs1553638927

Variant names:

• chr3-49422516-T-A
• rs1553638927
• ENST00000395338.7:c.-66A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-49422516-T-A
• chr3-49422516-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000395338.7(AMT):​c.-66A>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000147 in 1,360,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: AMT ENST00000395338.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.72
• Publications: 0 publications found

Genes affected

AMT (HGNC:473): (aminomethyltransferase) This gene encodes one of four critical components of the glycine cleavage system. Mutations in this gene have been associated with glycine encephalopathy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

NICN1 (HGNC:18317): (nicolin 1, tubulin polyglutamylase complex subunit) This protein encoded by this gene localizes to the nucleus and is expressed in numerous tissues including brain, testis, liver, and kidney. This refseq contains genomic sequence in its 3' UTR which is not supported by experimental evidence. Computer predictions indicate that this region of the 3' UTR contains hairpin-forming self-complementary sequence which is possibly excised after transcription. This gene has a pseudogene on chromosome X. [provided by RefSeq, Jul 2008]

ENSG00000283189 (HGNC:):

ACMG classification

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 (BayesDel_noAF=-0.25).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NICN1	NM_032316.3	c.*2317A>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000273598.8	NP_115692.1
AMT	NM_000481.4	c.-66A>T		upstream_gene_variant		ENST00000273588.9	NP_000472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NICN1	ENST00000273598.8	c.*2317A>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_032316.3	ENSP00000273598.4
ENSG00000283189	ENST00000636166.1	c.496-944A>T		intron_variant	Intron 4 of 10	5		ENSP00000490106.1
AMT	ENST00000273588.9	c.-66A>T		upstream_gene_variant		1	NM_000481.4	ENSP00000273588.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1360876 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 678624

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31298

American (AMR) AF: 0.00 AC: 0 AN: 39666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25096

East Asian (EAS) AF: 0.00 AC: 0 AN: 37854

South Asian (SAS) AF: 0.00 AC: 0 AN: 82206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5574

European-Non Finnish (NFE) AF: 0.00000194 AC: 2 AN: 1032146

Other (OTH) AF: 0.00 AC: 0 AN: 56888

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Benign	0.93
PhyloP100		3.7
PromoterAI		-0.41	Neutral

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: rs1553638927; hg19: chr3-49459949;