chr6-32129540-G-GAGACTTATGAGA

Variant names:

• chr6-32129540-G-GAGACTTATGAGA
• rs373328430
• NM_022110.4:c.229_240dupTCTCATAAGTCT

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM4 BP6 BS1 BS2

The NM_022110.4(FKBPL):​c.229_240dupTCTCATAAGTCT​(p.Ser80_His81insSerHisLysSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,614,196 control chromosomes in the GnomAD database, including 103 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0033 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (83 hom.)
• Consequence: FKBPL NM_022110.4 conservative_inframe_insertion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.00100
• Publications: 1 publications found

Genes affected

FKBPL (HGNC:13949): (FKBP prolyl isomerase like) The protein encoded by this gene has similarity to the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The encoded protein is thought to have a potential role in the induced radioresistance. Also it appears to have some involvement in the control of the cell cycle. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_022110.4.
• BP6: Variant 6-32129540-G-GAGACTTATGAGA is Benign according to our data. Variant chr6-32129540-G-GAGACTTATGAGA is described in ClinVar as Likely_benign. ClinVar VariationId is 3039678.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00327 (498/152308) while in subpopulation SAS AF = 0.0197 (95/4828). AF 95% confidence interval is 0.0165. There are 20 homozygotes in GnomAd4. There are 242 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022110.4. 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
	FKBPL	NM_022110.4	MANE Select	c.229_240dupTCTCATAAGTCT	p.Ser80_His81insSerHisLysSer	conservative_inframe_insertion	Exon 2 of 2	NP_071393.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBPL	ENST00000375156.4	TSL:1 MANE Select	c.229_240dupTCTCATAAGTCT	p.Ser80_His81insSerHisLysSer	conservative_inframe_insertion	Exon 2 of 2	ENSP00000364298.3	Q9UIM3
	FKBPL	ENST00000887777.1		c.229_240dupTCTCATAAGTCT	p.Ser80_His81insSerHisLysSer	conservative_inframe_insertion	Exon 2 of 2	ENSP00000557836.1
	FKBPL	ENST00000930347.1		c.229_240dupTCTCATAAGTCT	p.Ser80_His81insSerHisLysSer	conservative_inframe_insertion	Exon 2 of 2	ENSP00000600406.1

Frequencies

GnomAD3 genomes AF: 0.00314 AC: 478 AN: 152190 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00704 AC: 1770 AN: 251452 AF XY: 0.00702

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.0241

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00913

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000923

Gnomad OTH exome AF: 0.00668

GnomAD4 exome AF: 0.00303 AC: 4430 AN: 1461888 Hom.: 83 Cov.: 33 AF XY: 0.00351 AC XY: 2552 AN XY: 727246

African (AFR) AF: 0.000687 AC: 23 AN: 33480

American (AMR) AF: 0.0236 AC: 1054 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00111 AC: 29 AN: 26136

East Asian (EAS) AF: 0.00680 AC: 270 AN: 39700

South Asian (SAS) AF: 0.0195 AC: 1683 AN: 86258

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53420

Middle Eastern (MID) AF: 0.00693 AC: 40 AN: 5768

European-Non Finnish (NFE) AF: 0.000688 AC: 765 AN: 1112012

Other (OTH) AF: 0.00927 AC: 560 AN: 60392

GnomAD4 genome AF: 0.00327 AC: 498 AN: 152308 Hom.: 20 Cov.: 32 AF XY: 0.00325 AC XY: 242 AN XY: 74482

African (AFR) AF: 0.00132 AC: 55 AN: 41564

American (AMR) AF: 0.0127 AC: 194 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5186

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000926 AC: 63 AN: 68032

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00268 Hom.: 1

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FKBPL-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0010
Mutation Taster		=78/22	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs373328430; hg19: chr6-32097317;