6-158148854-T-C

Variant names:

• chr6-158148854-T-C
• rs9356399
• NM_032861.4:c.355+11A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032861.4(SERAC1):​c.355+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,575,790 control chromosomes in the GnomAD database, including 180,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14960 hom., cov: 33)
  • Exomes 𝑓: 0.48 (165598 hom.)
• Consequence: SERAC1 NM_032861.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.157
• Publications: 11 publications found

Genes affected

SERAC1 (HGNC:21061): (serine active site containing 1) The protein encoded by this gene is a phosphatidylglycerol remodeling protein found at the interface of mitochondria and endoplasmic reticula, where it mediates phospholipid exchange. The encoded protein plays a major role in mitochondrial function and intracellular cholesterol trafficking. Defects in this gene are a cause of 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL). Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Aug 2012]

SERAC1 Gene-Disease associations (from GenCC):

• 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, G2P
• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-158148854-T-C is Benign according to our data. Variant chr6-158148854-T-C is described in ClinVar as Benign. ClinVar VariationId is 139094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032861.4. 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
	SERAC1	NM_032861.4	MANE Select	c.355+11A>G		intron	N/A	NP_116250.3
	SERAC1	NR_073096.2		n.479+11A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERAC1	ENST00000647468.2	MANE Select	c.355+11A>G		intron	N/A	ENSP00000496731.1	Q96JX3-1
	SERAC1	ENST00000606965.5	TSL:1	n.355+11A>G		intron	N/A	ENSP00000475808.1	U3KQE4
	SERAC1	ENST00000607742.5	TSL:1	n.*189+11A>G		intron	N/A	ENSP00000475523.1	U3KQG3

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65294 AN: 152044 Hom.: 14933 Cov.: 33

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.446

GnomAD2 exomes AF: 0.481 AC: 117002 AN: 243458 AF XY: 0.479

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.667

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.421

Gnomad FIN exome AF: 0.456

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.499

GnomAD4 exome AF: 0.478 AC: 679924 AN: 1423628 Hom.: 165598 Cov.: 24 AF XY: 0.478 AC XY: 338929 AN XY: 709540

African (AFR) AF: 0.258 AC: 8401 AN: 32514

American (AMR) AF: 0.661 AC: 28450 AN: 43044

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 13589 AN: 25756

East Asian (EAS) AF: 0.491 AC: 19261 AN: 39260

South Asian (SAS) AF: 0.449 AC: 37187 AN: 82864

European-Finnish (FIN) AF: 0.455 AC: 24249 AN: 53250

Middle Eastern (MID) AF: 0.538 AC: 3058 AN: 5688

European-Non Finnish (NFE) AF: 0.479 AC: 518490 AN: 1082176

Other (OTH) AF: 0.461 AC: 27239 AN: 59076

GnomAD4 genome AF: 0.430 AC: 65357 AN: 152162 Hom.: 14960 Cov.: 33 AF XY: 0.432 AC XY: 32145 AN XY: 74388

African (AFR) AF: 0.267 AC: 11066 AN: 41516

American (AMR) AF: 0.596 AC: 9114 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1799 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2242 AN: 5186

South Asian (SAS) AF: 0.434 AC: 2095 AN: 4826

European-Finnish (FIN) AF: 0.453 AC: 4794 AN: 10576

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.483 AC: 32857 AN: 67984

Other (OTH) AF: 0.449 AC: 948 AN: 2112

Alfa AF: 0.472 Hom.: 9828

Bravo AF: 0.434

Asia WGS AF: 0.417 AC: 1449 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9356399; hg19: chr6-158569886; COSMIC: COSV65595966;