2-206159383-G-T

Variant names:

• chr2-206159383-G-T
• rs4147707
• NM_005006.7:c.-47C>A

Variant summary

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

The NM_005006.7(NDUFS1):​c.-47C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000196 in 560,240 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: NDUFS1 NM_005006.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346
• Publications: 10 publications found

Genes affected

NDUFS1 (HGNC:7707): (NADH:ubiquinone oxidoreductase core subunit S1) The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized. Mutations in this gene are associated with complex I deficiency. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

EEF1B2 (HGNC:3208): (eukaryotic translation elongation factor 1 beta 2) This gene encodes a translation elongation factor. The protein is a guanine nucleotide exchange factor involved in the transfer of aminoacylated tRNAs to the ribosome. Alternative splicing results in three transcript variants which differ only in the 5' UTR. [provided by RefSeq, Jul 2008]

EEF1B2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

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=-0.44).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005006.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFS1	NM_005006.7	MANE Select	c.-47C>A		5_prime_UTR	Exon 1 of 19	NP_004997.4
	NDUFS1	NM_001199981.2		c.-47C>A		5_prime_UTR	Exon 1 of 18	NP_001186910.1
	NDUFS1	NM_001199983.2		c.-126C>A		5_prime_UTR	Exon 1 of 18	NP_001186912.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFS1	ENST00000233190.11	TSL:1 MANE Select	c.-47C>A		5_prime_UTR	Exon 1 of 19	ENSP00000233190.5
	NDUFS1	ENST00000456284.5	TSL:4	n.-47C>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000395553.1
	NDUFS1	ENST00000440274.5	TSL:2	c.-47C>A		5_prime_UTR	Exon 1 of 18	ENSP00000409766.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152016 Hom.: 0 Cov.: 33

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: 0.0000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000245 AC: 10 AN: 408224 Hom.: 0 Cov.: 3 AF XY: 0.0000280 AC XY: 6 AN XY: 213934

African (AFR) AF: 0.00 AC: 0 AN: 11672

American (AMR) AF: 0.00 AC: 0 AN: 17434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12566

East Asian (EAS) AF: 0.00 AC: 0 AN: 29270

South Asian (SAS) AF: 0.00 AC: 0 AN: 38278

European-Finnish (FIN) AF: 0.000329 AC: 9 AN: 27358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1800

European-Non Finnish (NFE) AF: 0.00000407 AC: 1 AN: 245778

Other (OTH) AF: 0.00 AC: 0 AN: 24068

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152016 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74234

African (AFR) AF: 0.00 AC: 0 AN: 41370

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10578

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.1
DANN	Benign	0.68
PhyloP100		0.35
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs4147707; hg19: chr2-207024107;