chr13-98448293-T-C

Variant names:

• chr13-98448293-T-C
• rs12261
• NM_005766.4:c.3114T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005766.4(FARP1):​c.3114T>C​(p.Ser1038Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,612,630 control chromosomes in the GnomAD database, including 259,699 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 0.54 (22512 hom., cov: 33)
  • Exomes 𝑓: 0.57 (237187 hom.)
• Consequence: FARP1 NM_005766.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 28 publications found

Genes affected

FARP1 (HGNC:3591): (FERM, ARH/RhoGEF and pleckstrin domain protein 1) This gene encodes a protein containing a FERM (4.2, exrin, radixin, moesin) domain, a Dbl homology domain, and two pleckstrin homology domains. These domains are found in guanine nucleotide exchange factors and proteins that link the cytoskeleton to the cell membrane. The encoded protein functions in neurons to promote dendritic growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

STK24 (HGNC:11403): (serine/threonine kinase 24) This gene encodes a serine/threonine protein kinase that functions upstream of mitogen-activated protein kinase (MAPK) signaling. The encoded protein is cleaved into two chains by caspases; the N-terminal fragment (MST3/N) translocates to the nucleus and promotes programmed cells death. There is a pseudogene for this gene on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.127 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005766.4. 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
	FARP1	NM_005766.4	MANE Select	c.3114T>C	p.Ser1038Ser	synonymous	Exon 27 of 27	NP_005757.1	A0A2X0TVY0
	STK24	NM_001032296.4	MANE Select	c.*4880A>G		3_prime_UTR	Exon 11 of 11	NP_001027467.2	Q9Y6E0-2
	FARP1	NM_001286839.2		c.3207T>C	p.Ser1069Ser	synonymous	Exon 28 of 28	NP_001273768.1	C9JME2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARP1	ENST00000319562.11	TSL:1 MANE Select	c.3114T>C	p.Ser1038Ser	synonymous	Exon 27 of 27	ENSP00000322926.6	Q9Y4F1-1
	FARP1	ENST00000595437.5	TSL:1	c.3207T>C	p.Ser1069Ser	synonymous	Exon 28 of 28	ENSP00000471242.1	C9JME2
	STK24	ENST00000539966.6	TSL:1 MANE Select	c.*4880A>G		3_prime_UTR	Exon 11 of 11	ENSP00000442539.2	Q9Y6E0-2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82330 AN: 151980 Hom.: 22495 Cov.: 33

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.541

GnomAD2 exomes AF: 0.538 AC: 135237 AN: 251400 AF XY: 0.540

Gnomad AFR exome AF: 0.488

Gnomad AMR exome AF: 0.403

Gnomad ASJ exome AF: 0.558

Gnomad EAS exome AF: 0.559

Gnomad FIN exome AF: 0.629

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.562

GnomAD4 exome AF: 0.567 AC: 828766 AN: 1460532 Hom.: 237187 Cov.: 39 AF XY: 0.565 AC XY: 410292 AN XY: 726696

African (AFR) AF: 0.487 AC: 16289 AN: 33450

American (AMR) AF: 0.414 AC: 18511 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 14608 AN: 26130

East Asian (EAS) AF: 0.602 AC: 23900 AN: 39686

South Asian (SAS) AF: 0.462 AC: 39833 AN: 86230

European-Finnish (FIN) AF: 0.615 AC: 32846 AN: 53416

Middle Eastern (MID) AF: 0.548 AC: 3158 AN: 5760

European-Non Finnish (NFE) AF: 0.581 AC: 645452 AN: 1110794

Other (OTH) AF: 0.566 AC: 34169 AN: 60354

GnomAD4 genome AF: 0.542 AC: 82381 AN: 152098 Hom.: 22512 Cov.: 33 AF XY: 0.542 AC XY: 40331 AN XY: 74352

African (AFR) AF: 0.489 AC: 20279 AN: 41482

American (AMR) AF: 0.471 AC: 7209 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1954 AN: 3468

East Asian (EAS) AF: 0.567 AC: 2929 AN: 5164

South Asian (SAS) AF: 0.461 AC: 2225 AN: 4822

European-Finnish (FIN) AF: 0.633 AC: 6698 AN: 10576

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39205 AN: 67976

Other (OTH) AF: 0.540 AC: 1142 AN: 2116

Alfa AF: 0.563 Hom.: 48373

Bravo AF: 0.530

Asia WGS AF: 0.530 AC: 1840 AN: 3478

EpiCase AF: 0.584

EpiControl AF: 0.588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.5
DANN	Benign	0.45
PhyloP100		0.13
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: rs12261; hg19: chr13-99100547; COSMIC: COSV60339295; COSMIC: COSV60339295;