rs1937

Variant names:

• chr10-58385582-G-A
• NM_003201.3:c.35G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-58385582-G-A
• chr10-58385582-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003201.3(TFAM):​c.35G>A​(p.Ser12Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,418,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S12T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TFAM NM_003201.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569

Genes affected

TFAM (HGNC:11741): (transcription factor A, mitochondrial) This gene encodes a key mitochondrial transcription factor containing two high mobility group motifs. The encoded protein also functions in mitochondrial DNA replication and repair. Sequence polymorphisms in this gene are associated with Alzheimer's and Parkinson's diseases. There are pseudogenes for this gene on chromosomes 6, 7, and 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07547602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFAM	NM_003201.3	c.35G>A	p.Ser12Asn	missense_variant	Exon 1 of 7	ENST00000487519.6	NP_003192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAM	ENST00000487519.6	c.35G>A	p.Ser12Asn	missense_variant	Exon 1 of 7	1	NM_003201.3	ENSP00000420588.1
TFAM	ENST00000373895.7	c.35G>A	p.Ser12Asn	missense_variant	Exon 1 of 6	2		ENSP00000363002.3
TFAM	ENST00000373899.3	n.238G>A		non_coding_transcript_exon_variant	Exon 1 of 8	2
TFAM	ENST00000395377.2	c.-23G>A		upstream_gene_variant		2		ENSP00000378776.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1418764 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 701670

Gnomad4 AFR exome AF: 0.0000309

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000270

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.98	N;N
REVEL	Benign	0.039
Sift	Benign	0.16	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.0010	B;.
Vest4		0.051
MutPred		0.26		Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);
MVP		0.16
MPC		0.22
ClinPred		0.29	T
GERP RS		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.082
gMVP		0.42

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-60145342;