NM_013280.5:c.228C>T

Variant names:

• chr11-64116495-C-T
• rs200049740
• NM_013280.5:c.228C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_013280.5(FLRT1):​c.228C>T​(p.Pro76Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,613,980 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: FLRT1 NM_013280.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.270
• Publications: 0 publications found

Genes affected

FLRT1 (HGNC:3760): (fibronectin leucine rich transmembrane protein 1) This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. The family members may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. The encoded protein shares sequence similarity with two other family members, FLRT2 and FLRT3. This gene is expressed in kidney and brain. [provided by RefSeq, Jul 2008]

MACROD1 (HGNC:29598): (mono-ADP ribosylhydrolase 1) Enables ADP-ribosylglutamate hydrolase activity and deacetylase activity. Involved in cellular response to DNA damage stimulus; peptidyl-glutamate ADP-deribosylation; and purine nucleoside metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-64116495-C-T is Benign according to our data. Variant chr11-64116495-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1107240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.27 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013280.5. 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
	FLRT1	NM_013280.5	MANE Select	c.228C>T	p.Pro76Pro	synonymous	Exon 3 of 3	NP_037412.2
	MACROD1	NM_014067.4	MANE Select	c.517+34744G>A		intron	N/A	NP_054786.2
	FLRT1	NM_001384466.1		c.228C>T	p.Pro76Pro	synonymous	Exon 3 of 3	NP_001371395.1	Q9NZU1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT1	ENST00000682287.1	MANE Select	c.228C>T	p.Pro76Pro	synonymous	Exon 3 of 3	ENSP00000507207.1	Q9NZU1-2
	FLRT1	ENST00000246841.3	TSL:1	c.228C>T	p.Pro76Pro	synonymous	Exon 2 of 2	ENSP00000246841.3	Q9NZU1-2
	MACROD1	ENST00000255681.7	TSL:1 MANE Select	c.517+34744G>A		intron	N/A	ENSP00000255681.6	Q9BQ69

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000291 AC: 73 AN: 250900 AF XY: 0.000339

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.000432

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000235 AC: 343 AN: 1461654 Hom.: 1 Cov.: 30 AF XY: 0.000248 AC XY: 180 AN XY: 727116

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000246 AC: 11 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86256

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53288

Middle Eastern (MID) AF: 0.00676 AC: 39 AN: 5768

European-Non Finnish (NFE) AF: 0.000210 AC: 234 AN: 1111936

Other (OTH) AF: 0.000596 AC: 36 AN: 60386

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.000322 AC XY: 24 AN XY: 74488

African (AFR) AF: 0.000168 AC: 7 AN: 41572

American (AMR) AF: 0.000523 AC: 8 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68034

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000360 Hom.: 1

Bravo AF: 0.000272

EpiCase AF: 0.000709

EpiControl AF: 0.000830

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Peripheral neuropathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.87
PhyloP100		-0.27
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.2
Mutation Taster		=99/1	polymorphism

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: rs200049740; hg19: chr11-63883967;