NM_015123.3:c.2677G>T

Variant names:

• chr3-69181073-C-A
• rs192984298
• NM_015123.3:c.2677G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_015123.3(FRMD4B):​c.2677G>T​(p.Ala893Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,613,968 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (6 hom.)
• Consequence: FRMD4B NM_015123.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.57
• Publications: 6 publications found

Genes affected

FRMD4B (HGNC:24886): (FERM domain containing 4B) This gene encodes a GRP1-binding protein which contains a FERM protein interaction domain as well as two coiled coil domains. This protein may play a role as a scaffolding protein. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1034182).
• BP6: Variant 3-69181073-C-A is Benign according to our data. Variant chr3-69181073-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 782988.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015123.3. 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
	FRMD4B	NM_015123.3	MANE Select	c.2677G>T	p.Ala893Ser	missense	Exon 21 of 23	NP_055938.2	Q9Y2L6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4B	ENST00000398540.8	TSL:1 MANE Select	c.2677G>T	p.Ala893Ser	missense	Exon 21 of 23	ENSP00000381549.3	Q9Y2L6-1
	FRMD4B	ENST00000478263.5	TSL:1	c.1633G>T	p.Ala545Ser	missense	Exon 11 of 13	ENSP00000418682.1	E9PGA7
	FRMD4B	ENST00000863518.1		c.2617G>T	p.Ala873Ser	missense	Exon 21 of 23	ENSP00000533577.1

Frequencies

GnomAD3 genomes AF: 0.00146 AC: 222 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00144 AC: 360 AN: 249226 AF XY: 0.00144

Gnomad AFR exome AF: 0.000258

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00330

Gnomad NFE exome AF: 0.00237

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00171 AC: 2506 AN: 1461708 Hom.: 6 Cov.: 37 AF XY: 0.00172 AC XY: 1253 AN XY: 727136

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00449 AC: 240 AN: 53402

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00195 AC: 2163 AN: 1111866

Other (OTH) AF: 0.00139 AC: 84 AN: 60374

GnomAD4 genome AF: 0.00146 AC: 222 AN: 152260 Hom.: 0 Cov.: 32 AF XY: 0.00146 AC XY: 109 AN XY: 74436

African (AFR) AF: 0.000217 AC: 9 AN: 41550

American (AMR) AF: 0.000458 AC: 7 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00321 AC: 34 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00246 AC: 167 AN: 68024

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00193 Hom.: 1

Bravo AF: 0.00112

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000246 AC: 1

ESP6500EA AF: 0.00227 AC: 19

ExAC AF: 0.00160 AC: 194

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.10	T
MetaSVM	Uncertain	0.64	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.90	N
REVEL	Uncertain	0.57
Sift	Uncertain	0.014	D
Sift4G	Benign	0.077	T
Polyphen		0.99	D
Vest4		0.79
MVP		0.62
MPC		0.19
ClinPred		0.057	T
GERP RS		5.8
Varity_R		0.21
gMVP		0.40
Mutation Taster		=85/15	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: rs192984298; hg19: chr3-69230224;