15-30942802-G-C

Variant names:

• chr15-30942802-G-C
• rs3512
• NM_014967.5:c.*1240G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014967.5. 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
	FAN1	NM_014967.5	MANE Select	c.*1240G>C		3_prime_UTR	Exon 15 of 15	NP_055782.3	Q9Y2M0-1
	MTMR10	NM_017762.3	MANE Select	c.1731+88C>G		intron	N/A	NP_060232.2	X5D963

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAN1	ENST00000362065.9	TSL:1 MANE Select	c.*1240G>C		3_prime_UTR	Exon 15 of 15	ENSP00000354497.4	Q9Y2M0-1
	MTMR10	ENST00000435680.6	TSL:1 MANE Select	c.1731+88C>G		intron	N/A	ENSP00000402537.1	Q9NXD2-1
	FAN1	ENST00000565280.5	TSL:1	n.*3135G>C		non_coding_transcript_exon	Exon 16 of 16	ENSP00000455573.1	H3BQ24

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

African (AFR) AF: 0.195 AC: 4945 AN: 25350

American (AMR) AF: 0.169 AC: 3843 AN: 22748

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 4978 AN: 18896

East Asian (EAS) AF: 0.0179 AC: 601 AN: 33662

South Asian (SAS) AF: 0.224 AC: 13325 AN: 59476

European-Finnish (FIN) AF: 0.352 AC: 16038 AN: 45614

Middle Eastern (MID) AF: 0.252 AC: 883 AN: 3506

European-Non Finnish (NFE) AF: 0.333 AC: 302483 AN: 908414

Other (OTH) AF: 0.284 AC: 14025 AN: 49370

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

African (AFR) AF: 0.195 AC: 8088 AN: 41496

American (AMR) AF: 0.195 AC: 2980 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 886 AN: 3470

East Asian (EAS) AF: 0.0143 AC: 74 AN: 5178

South Asian (SAS) AF: 0.221 AC: 1066 AN: 4818

European-Finnish (FIN) AF: 0.344 AC: 3632 AN: 10570

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22391 AN: 67956

Other (OTH) AF: 0.261 AC: 552 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.97
DANN	Benign	0.56
PhyloP100		0.23
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: rs3512; hg19: chr15-31235005; COSMIC: COSV58728289; COSMIC: COSV58728289;