5-131171208-TTG-T

Variant names:

• chr5-131171208-TTG-T
• rs33949871
• NM_181705.4:c.18+173_18+174delTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_181705.4(LYRM7):​c.18+173_18+174delTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,846 control chromosomes in the GnomAD database, including 6,231 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (6231 hom., cov: 30)
• Consequence: LYRM7 NM_181705.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.356
• Publications: 0 publications found

Genes affected

LYRM7 (HGNC:28072): (LYR motif containing 7) Inner mitochondrial membrane complex III (CIII) is the main enzyme complex in the mitochondrial respiratory chain, and Rieske Fe-S protein (UQCRFS1) is the last catalytic subunit added to the complex. The protein encoded by this gene is a nuclear-encoded mitochondrial matrix protein that stabilizes UQCRFS1 and chaperones it to the CIII complex. Defects in this gene are a cause of mitochondrial complex III deficiency, nuclear type 8. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

HINT1 (HGNC:4912): (histidine triad nucleotide binding protein 1) This gene encodes a protein that hydrolyzes purine nucleotide phosphoramidates substrates, including AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester, and AMP-NH2. The encoded protein interacts with these substrates via a histidine triad motif. This gene is considered a tumor suppressor gene. In addition, mutations in this gene can cause autosomal recessive neuromyotonia and axonal neuropathy. There are several related pseudogenes on chromosome 7. Several transcript variants have been observed. [provided by RefSeq, Dec 2015]

HINT1 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Gamstorp-Wohlfart syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-131171208-TTG-T is Benign according to our data. Variant chr5-131171208-TTG-T is described in ClinVar as Benign. ClinVar VariationId is 1252214.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181705.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYRM7	NM_181705.4	MANE Select	c.18+173_18+174delTG		intron	N/A	NP_859056.2	Q5U5X0
	LYRM7	NM_001293735.2		c.18+173_18+174delTG		intron	N/A	NP_001280664.1	D6RBV5
	LYRM7	NR_121658.2		n.95+173_95+174delTG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYRM7	ENST00000379380.9	TSL:1 MANE Select	c.18+171_18+172delTG		intron	N/A	ENSP00000368688.4	Q5U5X0
	LYRM7	ENST00000855899.1		c.18+171_18+172delTG		intron	N/A	ENSP00000525958.1
	LYRM7	ENST00000931593.1		c.12+177_12+178delTG		intron	N/A	ENSP00000601652.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27281 AN: 151728 Hom.: 6215 Cov.: 30

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.00916

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.0391

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.180 AC: 27334 AN: 151846 Hom.: 6231 Cov.: 30 AF XY: 0.174 AC XY: 12944 AN XY: 74266

African (AFR) AF: 0.537 AC: 22168 AN: 41268

American (AMR) AF: 0.0919 AC: 1403 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3468

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5170

South Asian (SAS) AF: 0.0485 AC: 233 AN: 4808

European-Finnish (FIN) AF: 0.00916 AC: 97 AN: 10592

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.0391 AC: 2658 AN: 67954

Other (OTH) AF: 0.158 AC: 334 AN: 2112

Alfa AF: 0.122 Hom.: 458

Bravo AF: 0.203

Asia WGS AF: 0.0640 AC: 225 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs33949871; hg19: chr5-130506901;