NM_001394565.1:c.93C>T

Variant names:

• chr1-46668230-G-A
• rs1676528032
• NM_001394565.1:c.93C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001394565.1(ATPAF1):​c.93C>T​(p.Ser31Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000082 in 1,219,120 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: not found (cov: 31)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: ATPAF1 NM_001394565.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847
• Publications: 0 publications found

Genes affected

ATPAF1 (HGNC:18803): (ATP synthase mitochondrial F1 complex assembly factor 1) This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 beta subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.847 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATPAF1	NM_001394565.1	c.93C>T	p.Ser31Ser	synonymous_variant	Exon 1 of 9	ENST00000574428.6	NP_001381494.1
ATPAF1	NM_022745.6	c.162C>T	p.Ser54Ser	synonymous_variant	Exon 1 of 9		NP_073582.3
ATPAF1	NM_001042546.2	c.162C>T	p.Ser54Ser	synonymous_variant	Exon 1 of 7		NP_001036011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATPAF1	ENST00000574428.6	c.93C>T	p.Ser31Ser	synonymous_variant	Exon 1 of 9	1	NM_001394565.1	ENSP00000459167.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.20e-7 AC: 1 AN: 1219120 Hom.: 0 Cov.: 34 AF XY: 0.00000168 AC XY: 1 AN XY: 595270

⚠️ 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: 24700

American (AMR) AF: 0.00 AC: 0 AN: 17772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19482

East Asian (EAS) AF: 0.00 AC: 0 AN: 26250

South Asian (SAS) AF: 0.00 AC: 0 AN: 54712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3502

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 993064

Other (OTH) AF: 0.00 AC: 0 AN: 49422

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.96
PhyloP100		0.85
PromoterAI		-0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
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: rs1676528032; hg19: chr1-47133902;