rs2955795

Variant names:

• chr15-30937217-T-C
• rs2955795
• NM_014967.5:c.3015T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014967.5(FAN1):​c.3015T>C​(p.His1005His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,613,064 control chromosomes in the GnomAD database, including 174,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (13700 hom., cov: 32)
  • Exomes 𝑓: 0.46 (160347 hom.)
• Consequence: FAN1 NM_014967.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.817
• Publications: 24 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-30937217-T-C is Benign according to our data. Variant chr15-30937217-T-C is described in ClinVar as Benign. ClinVar VariationId is 260491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.817 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 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.3015T>C	p.His1005His	synonymous	Exon 14 of 15	NP_055782.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAN1	ENST00000362065.9	TSL:1 MANE Select	c.3015T>C	p.His1005His	synonymous	Exon 14 of 15	ENSP00000354497.4
	FAN1	ENST00000565280.5	TSL:1	n.*1856T>C		non_coding_transcript_exon	Exon 15 of 16	ENSP00000455573.1
	FAN1	ENST00000565280.5	TSL:1	n.*1856T>C		3_prime_UTR	Exon 15 of 16	ENSP00000455573.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59809 AN: 151922 Hom.: 13685 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.394

GnomAD2 exomes AF: 0.486 AC: 122200 AN: 251342 AF XY: 0.485

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.579

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.851

Gnomad FIN exome AF: 0.472

Gnomad NFE exome AF: 0.441

Gnomad OTH exome AF: 0.482

GnomAD4 exome AF: 0.459 AC: 670839 AN: 1461024 Hom.: 160347 Cov.: 39 AF XY: 0.460 AC XY: 334310 AN XY: 726866

African (AFR) AF: 0.153 AC: 5112 AN: 33468

American (AMR) AF: 0.566 AC: 25281 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 12939 AN: 26124

East Asian (EAS) AF: 0.858 AC: 34079 AN: 39700

South Asian (SAS) AF: 0.514 AC: 44339 AN: 86196

European-Finnish (FIN) AF: 0.471 AC: 25139 AN: 53402

Middle Eastern (MID) AF: 0.416 AC: 2395 AN: 5762

European-Non Finnish (NFE) AF: 0.444 AC: 493945 AN: 1111342

Other (OTH) AF: 0.458 AC: 27610 AN: 60348

GnomAD4 genome AF: 0.394 AC: 59830 AN: 152040 Hom.: 13700 Cov.: 32 AF XY: 0.405 AC XY: 30081 AN XY: 74344

African (AFR) AF: 0.171 AC: 7108 AN: 41478

American (AMR) AF: 0.498 AC: 7603 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3468

East Asian (EAS) AF: 0.851 AC: 4400 AN: 5170

South Asian (SAS) AF: 0.540 AC: 2605 AN: 4826

European-Finnish (FIN) AF: 0.473 AC: 4981 AN: 10538

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29945 AN: 67970

Other (OTH) AF: 0.400 AC: 844 AN: 2112

Alfa AF: 0.423 Hom.: 11151

Bravo AF: 0.387

Asia WGS AF: 0.629 AC: 2187 AN: 3478

EpiCase AF: 0.440

EpiControl AF: 0.441

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Karyomegalic interstitial nephritis (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.46
DANN	Benign	0.65
PhyloP100		-0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs2955795; hg19: chr15-31229420; COSMIC: COSV58727620; COSMIC: COSV58727620;