11-71473279-AAACCGTACCCTTCGG-A

Position:

• chr11-71473279-AAACCGTACCCTTCGG-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_018161.5(NADSYN1):​c.463_477del​(p.Thr155_Gly159del) variant causes a inframe deletion, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 34)
• Consequence: NADSYN1 NM_018161.5 inframe_deletion, splice_region
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.72

Genes affected

NADSYN1 (HGNC:29832): (NAD synthetase 1) Nicotinamide adenine dinucleotide (NAD) is a coenzyme in metabolic redox reactions, a precursor for several cell signaling molecules, and a substrate for protein posttranslational modifications. NAD synthetase (EC 6.3.5.1) catalyzes the final step in the biosynthesis of NAD from nicotinic acid adenine dinucleotide (NaAD).[supplied by OMIM, Apr 2004]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_018161.5.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NADSYN1	NM_018161.5	c.463_477del	p.Thr155_Gly159del	inframe_deletion, splice_region_variant	7/21	ENST00000319023.7	NP_060631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NADSYN1	ENST00000319023.7	c.463_477del	p.Thr155_Gly159del	inframe_deletion, splice_region_variant	7/21	1	NM_018161.5	ENSP00000326424	P1
NADSYN1	ENST00000528509.5	c.463_477del	p.Thr155_Gly159del	inframe_deletion, splice_region_variant, NMD_transcript_variant	7/10	1		ENSP00000433472
NADSYN1	ENST00000525200.5	c.363_377del	p.Thr122_Gly126del	inframe_deletion, splice_region_variant, NMD_transcript_variant	6/21	2		ENSP00000432129
NADSYN1	ENST00000529120.5			splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000437220

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

NADSYN1-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 27, 2024

The NADSYN1 c.463_477del15 variant is predicted to result in an in-frame deletion (p.Thr155_Gly159del). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-71184325;