15-30942802-G-C

Position:

• chr15-30942802-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014967.5(FAN1):​c.*1240G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,319,134 control chromosomes in the GnomAD database, including 64,616 homozygotes. 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: 𝑓 0.26 (5820 hom., cov: 32)
  • Exomes 𝑓: 0.31 (58796 hom.)
• Consequence: FAN1 NM_014967.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227

Genes affected

FAN1 (HGNC:29170): (FANCD2 and FANCI associated nuclease 1) This gene plays a role in DNA interstrand cross-link repair and encodes a protein with 5' flap endonuclease and 5'-3' exonuclease activity. Mutations in this gene cause karyomegalic interstitial nephritis. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Feb 2016]

MTMR10 (HGNC:25999): (myotubularin related protein 10) Predicted to enable phosphatidylinositol-3-phosphatase activity. Predicted to be involved in phosphatidylinositol dephosphorylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MTMR10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAN1	NM_014967.5	c.*1240G>C		3_prime_UTR_variant	15/15	ENST00000362065.9	NP_055782.3
MTMR10	NM_017762.3	c.1731+88C>G		intron_variant		ENST00000435680.6	NP_060232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAN1	ENST00000362065.9	c.*1240G>C		3_prime_UTR_variant	15/15	1	NM_014967.5	ENSP00000354497.4
MTMR10	ENST00000435680.6	c.1731+88C>G		intron_variant		1	NM_017762.3	ENSP00000402537.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40071 AN: 151980 Hom.: 5818 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.309 AC: 361121 AN: 1167036 Hom.: 58796 Cov.: 16 AF XY: 0.308 AC XY: 176418 AN XY: 573382

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.0179

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.264 AC: 40079 AN: 152098 Hom.: 5820 Cov.: 32 AF XY: 0.259 AC XY: 19294 AN XY: 74352

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.261

Alfa AF: 0.191 Hom.: 411

Bravo AF: 0.251

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.97
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs3512; hg19: chr15-31235005; COSMIC: COSV58728289; COSMIC: COSV58728289;