rs199625765

Variant names:

• chr6-158111350-T-C
• rs199625765
• NM_032861.4:c.*16A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032861.4(SERAC1):​c.*16A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,565,208 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00097 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (4 hom.)
• Consequence: SERAC1 NM_032861.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.79
• Publications: 2 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: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000306953 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-158111350-T-C is Benign according to our data. Variant chr6-158111350-T-C is described in ClinVar as Benign. ClinVar VariationId is 215138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.*16A>G		3_prime_UTR	Exon 17 of 17	NP_116250.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERAC1	ENST00000647468.2	MANE Select	c.*16A>G		3_prime_UTR	Exon 17 of 17	ENSP00000496731.1	Q96JX3-1
	SERAC1	ENST00000607742.5	TSL:1	n.*3259A>G		non_coding_transcript_exon	Exon 15 of 15	ENSP00000475523.1	U3KQG3
	SERAC1	ENST00000607742.5	TSL:1	n.*3259A>G		3_prime_UTR	Exon 15 of 15	ENSP00000475523.1	U3KQG3

Frequencies

GnomAD3 genomes AF: 0.000972 AC: 148 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00119 AC: 253 AN: 212164 AF XY: 0.00109

Gnomad AFR exome AF: 0.000192

Gnomad AMR exome AF: 0.000124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00583

Gnomad NFE exome AF: 0.00125

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00107 AC: 1506 AN: 1412876 Hom.: 4 Cov.: 29 AF XY: 0.00101 AC XY: 706 AN XY: 700182

African (AFR) AF: 0.000129 AC: 4 AN: 31002

American (AMR) AF: 0.000151 AC: 5 AN: 33142

Ashkenazi Jewish (ASJ) AF: 0.0000424 AC: 1 AN: 23606

East Asian (EAS) AF: 0.00 AC: 0 AN: 39236

South Asian (SAS) AF: 0.00 AC: 0 AN: 78456

European-Finnish (FIN) AF: 0.00605 AC: 306 AN: 50592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5482

European-Non Finnish (NFE) AF: 0.00101 AC: 1105 AN: 1093068

Other (OTH) AF: 0.00146 AC: 85 AN: 58292

GnomAD4 genome AF: 0.000972 AC: 148 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.00111 AC XY: 83 AN XY: 74486

African (AFR) AF: 0.000120 AC: 5 AN: 41578

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00499 AC: 53 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00131 AC: 89 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000983 Hom.: 0

Bravo AF: 0.000582

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.42
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs199625765; hg19: chr6-158532382; COSMIC: COSV65596808; COSMIC: COSV65596808;