NM_001126334.1:c.1160G>C

Variant names:

• chr9-65283218-C-G
• NM_001126334.1:c.1160G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001126334.1(FOXD4L5):​c.1160G>C​(p.Ser387Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000042 (0 hom., cov: 11)
  • Exomes 𝑓: 0.000026 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXD4L5 NM_001126334.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87
• Publications: 0 publications found

Genes affected

FOXD4L5 (HGNC:18522): (forkhead box D4 like 5) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in anatomical structure morphogenesis; cell differentiation; and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18787491).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126334.1. 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
	FOXD4L5	NM_001126334.1	MANE Select	c.1160G>C	p.Ser387Thr	missense	Exon 1 of 1	NP_001119806.1	Q5VV16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXD4L5	ENST00000377420.1	TSL:6 MANE Select	c.1160G>C	p.Ser387Thr	missense	Exon 1 of 1	ENSP00000366637.1	Q5VV16

Frequencies

GnomAD3 genomes AF: 0.0000416 AC: 4 AN: 96102 Hom.: 0 Cov.: 11

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000563

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000210

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000256 AC: 35 AN: 1365348 Hom.: 2 Cov.: 27 AF XY: 0.0000235 AC XY: 16 AN XY: 680470

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000325 AC: 1 AN: 30796

American (AMR) AF: 0.00 AC: 0 AN: 41246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25218

East Asian (EAS) AF: 0.00 AC: 0 AN: 34714

South Asian (SAS) AF: 0.00 AC: 0 AN: 82618

European-Finnish (FIN) AF: 0.000513 AC: 25 AN: 48706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3948

European-Non Finnish (NFE) AF: 0.00000480 AC: 5 AN: 1041814

Other (OTH) AF: 0.0000711 AC: 4 AN: 56288

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000255013), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000416 AC: 4 AN: 96214 Hom.: 0 Cov.: 11 AF XY: 0.0000885 AC XY: 4 AN XY: 45190

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26002

American (AMR) AF: 0.00 AC: 0 AN: 8628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2516

East Asian (EAS) AF: 0.00 AC: 0 AN: 2134

South Asian (SAS) AF: 0.00 AC: 0 AN: 2008

European-Finnish (FIN) AF: 0.000563 AC: 3 AN: 5332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.0000210 AC: 1 AN: 47574

Other (OTH) AF: 0.00 AC: 0 AN: 1122

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.0092	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.27	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.99	T
Polyphen		0.95	P
Vest4		0.28
MutPred		0.12		Gain of glycosylation at S387 (P = 0.0841)
MVP		0.088
ClinPred		0.29	T
GERP RS		1.1
Varity_R		0.045
gMVP		0.013
Mutation Taster		=98/2	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

hg19: chr9-70176824;