NM_019095.6:c.54T>G

Variant names:

• chr20-6006300-T-G
• rs1600339324
• NM_019095.6:c.54T>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_019095.6(CRLS1):​c.54T>G​(p.Ala18Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRLS1 NM_019095.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.21
• Publications: 0 publications found

Genes affected

CRLS1 (HGNC:16148): (cardiolipin synthase 1) This gene encodes a member of the CDP-alcohol phosphatidyltransferase class-I family of proteins. The encoded enzyme catalyzes the synthesis of cardiolipin, a phospholipid component of mitochondrial membranes that is critical for mitochondrial function. [provided by RefSeq, Apr 2016]

ENSG00000286235 (HGNC:):

MCM8-AS1 (HGNC:51230): (MCM8 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-6006300-T-G is Benign according to our data. Variant chr20-6006300-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 727712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.21 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019095.6. 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
	CRLS1	NM_019095.6	MANE Select	c.54T>G	p.Ala18Ala	synonymous	Exon 1 of 7	NP_061968.1	Q9UJA2-1
	CRLS1	NM_001323563.2		c.-342T>G		5_prime_UTR	Exon 1 of 7	NP_001310492.1
	CRLS1	NM_001323562.2		c.-28+189T>G		intron	N/A	NP_001310491.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRLS1	ENST00000378863.9	TSL:1 MANE Select	c.54T>G	p.Ala18Ala	synonymous	Exon 1 of 7	ENSP00000368140.4	Q9UJA2-1
	CRLS1	ENST00000452938.5	TSL:1	c.54T>G	p.Ala18Ala	synonymous	Exon 1 of 6	ENSP00000416770.1	Q6NTG3
	ENSG00000286235	ENST00000652720.1		c.2431-3475T>G		intron	N/A	ENSP00000498784.1	A0A494C100

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000173 AC: 2 AN: 1154676 Hom.: 0 Cov.: 29 AF XY: 0.00000179 AC XY: 1 AN XY: 559276

⚠️ 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: 23764

American (AMR) AF: 0.00 AC: 0 AN: 13208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16342

East Asian (EAS) AF: 0.00 AC: 0 AN: 25926

South Asian (SAS) AF: 0.00 AC: 0 AN: 39564

European-Finnish (FIN) AF: 0.0000404 AC: 1 AN: 24736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3194

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 961638

Other (OTH) AF: 0.00 AC: 0 AN: 46304

⚠️ 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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.31
PhyloP100		-3.2
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs1600339324; hg19: chr20-5986946;